Original Article
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; 325:105-109July 11, 1991
- Abstract
Background.
It is uncertain whether Plasmodium falciparum malaria is more frequent or more severe in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection and whether P. falciparum infection accelerates the progression of HIV-related disease.
Methods.
We conducted a prospective, longitudinal cohort study in Kinshasa, Zaire. Two hundred sixty children 5 to 9 months of age who had been born to HIV-1—seropositive mothers and 327 children of the same age who had been born to seronegative mothers were monitored intensively for malaria over a 13-month period. All episodes of fever were evaluated with blood smears for malaria, and children found to be infected with P. falciparum were treated with a standard regimen of oral quinine.
Results.
A total of 2899 fevers were evaluated, with 271 cases of malaria identified. No statistically significant differences were found in the incidence, severity, or response to therapy of malaria among four well-defined groups of children: those with the acquired immunodeficiency syndrome (AIDS), those who were HIV-1—seropositive throughout the study, those who were born to HIV-1—seropositive mothers but reverted to seronegative, and those who were seronegative throughout the study. During the 13-month period the incidence of malaria in the 36 children with HIV infection in whom AIDS developed was lower, although not significantly so, than in the 37 in whom AIDS did not develop.
Conclusions.
In this study malaria was not more frequent or more severe in children with progressive HIV-1 infection and malaria did not appear to accelerate the rate of progression of HIV-1 disease. (N Engl J Med 1991; 325:105–9.)
Media in This Article
Table 1
Outcome and Duration of Follow-up of Study Children, According to HIV Status, from August 1987 to August 1988.Table 2
Incidence of Malaria in Study Children According to HIV Status.*Article Activity
- Article
THE epidemic of human immunodeficiency virus type 1 (HIV-1) infection in areas of the tropics where Plasmodium falciparum is endemic has generated serious concern about potential interactions between the two infections.1 , 2 Since the cellular immune system is critical to protection against malaria,3 , 4 it is biologically plausible that P. falciparum malaria could occur more frequently or be more severe in HIV-infected persons with profound CD4 lymphocyte depletion. Conversely, since P. falciparum infection is known to cause a transient decrease in T-lymphocyte subsets (notably CD4 and CD8),3 , 4 it has been postulated that repeated malarial infection may accelerate the progression of HIV-related disease.1 , 2 , 5
To date, however, a number of studies in pediatric and adult emergency room patients, hospitalized children, pregnant women, healthy adults, and ill adults in Zaire and Zambia have failed to demonstrate a direct association between infection with HIV-1 and P. falciparum.6 7 8 9 10 11 These cross-sectional studies, in which single blood samples were collected from various groups and tested for HIV-1 antibodies and malarial parasites, could be conducted rapidly and at relatively low cost. Longitudinal studies of large groups are needed, however, to assess the incidence and severity of malaria in patients with clinically advanced HIV-1 infection and to evaluate whether P. falciparum infection accelerates the progression of HIV-related disease.1 , 2 , 12 , 13
At Mama Yemo Hospital in Kinshasa, Zaire, pediatric patients are at high risk for both HIV-1 infection and severe malaria. Recent studies at this institution have demonstrated a rate of HIV-1 seropositivity among delivering mothers of 5.6 percent and a rate of perinatal HIV-1 transmission of 39 percent.14 In addition, 38 percent of all pediatric admissions and 13 percent of all deaths in children have been attributed to malaria.15 Since the effects of any proved association between HIV-1 and malaria could be particularly devastating in this population, we studied the incidence, severity, and response to therapy of malaria in a large cohort of children who were enrolled in a study of the natural history of perinatally acquired HIV-1 infection at Mama Yemo Hospital.14
Methods
Study of Perinatal HIV-1 Transmission
The methods used in the study of perinatal transmission of HIV-1 have been described in full elsewhere.14 Briefly, 329 mothers seropositive for HIV-1 and 337 seronegative control mothers matched for age and parity were identified while in active labor at Mama Yemo Hospital between December 1986 and April 1987. The 337 children of the seropositive mothers (including eight sets of twins) and the 341 children of the seronegative mothers (including four sets of twins) were then followed at monthly intervals, with additional visits when they became ill. All clinical care, medications, immunizations, and transportation to and from the study clinic were provided free of charge, which contributed to a rate of loss to follow-up of only 4 percent for the first 18 months of the study.16
The clinical evolution of HIV-1 infection in children born to seropositive mothers was measured with a monthly score for the acquired immunodeficiency syndrome (AIDS) based on the World Health Organization (WHO) clinical case definition of pediatric AIDS in Africa.17 Points were assigned for major criteria (chronic fever, persistent diarrhea, and failure to thrive) and minor criteria (generalized lymphadenopathy, oral—pharyngeal candidiasis after six months of age, pneumonia, and generalized papular dermatitis); children with 10 or more points were considered to have AIDS.14 The WHO clinical case definition, which had been validated earlier in children in Kinshasa,18 was used because the laboratory facilities needed to diagnose various infections and cancers that are included in the AIDS case definition of the Centers for Disease Control19 are either inadequate or unavailable in Kinshasa.
Blood samples obtained from the mothers during delivery and from their children at 12 and 18 months of age were screened for HIV-1 antibodies by enzyme-linked immunosorbent assay (ELISA; Wellcozyme, Burroughs Wellcome, London); those that were reactive on a second ELISA were confirmed by Western blot analysis (Dupont, Geneva).20 Cord-blood cultures for the isolation of HIV-121 were performed on samples from 64 randomly selected seropositive infants.14
P. falciparum Malaria Study
As of August 1987, 260 children born to seropositive mothers (62 other children had died, and 15 were lost to follow-up) and 327 children born to seronegative mothers (5 others had died, and 9 were lost to follow-up) remained in the perinatal study. The leading causes of death among the children born to seropositive mothers were prematurity (31 percent), diarrhea (31 percent), pneumonia (21 percent), and meningitis (13 percent).14 The study children were monitored intensively for malaria from August 1987 through August 1988. In August 1987 the children ranged from five to nine months old, an age at which most African children have lost any protection from maternally acquired antimalarial antibodies.22 , 23 Since naturally acquired immunity to malaria is relatively weak in younger children, the malaria study was conducted during the period in which the children were at greatest risk for malaria-related morbidity and mortality.15
During the 13-month study period, careful histories of fever were taken in the local language during all routine monthly visits. In addition, mothers were instructed to bring their children promptly to the study clinic whenever fever developed, with transportation to and from the hospital provided free of charge. Axillary temperatures were taken during all clinic visits, and thick blood smears for malaria were obtained from children with either a history of fever in the previous 48 hours or an axillary temperature of ≥37.3°C. Malaria smears were examined immediately by a trained microscopist, and children found to be infected with asexual P. falciparum parasites were given a diagnosis of malaria.
The response to antimalarial therapy was monitored closely from September 1987 through August 1988. Children with malaria who did not require intravenous therapy were treated with oral quinine sulfate (12.5 mg per kilogram of body weight every 12 hours for 3 days). This regimen was based on standard malaria therapy at Mama Yemo Hospital and was supported by a 1987 study in which a three-day regimen of quinine proved highly effective in producing a clinical and parasitologic cure in children hospitalized with moderate-to-severe malaria.24
Children with malaria were given their first dose of quinine by the nurses in the study clinic. Mothers were instructed to give the remaining five doses at home, to record the dates and times of quinine administration on a standardized form, and to bring their children and the completed forms back to the clinic 7 and 14 days later. At each follow-up visit, clinical assessments were performed and smears were studied for malaria; children who remained infected with P. falciparum on day 7 or 14 were treated with an age-adjusted dose of sulfadoxine—pyrimethamine (Fansidar).
All positive smears for malaria and 10 percent of the negative smears were reviewed by a second microscopist; the concordance of the two microscopists was 93.4 percent for positive smears and more than 99 percent for negative smears. For positive smears, we calculated the density of parasitemia by counting asexual parasites against 100 to 300 white cells on Giemsa-stained thick blood films, assuming a standard leukocyte count of 6000 per microliter of blood.25
Definitions of HIV Status
Children born to seropositive mothers were defined as being infected with HIV-1 if they were seropositive at both 12 and 18 months of age, if cord blood was positive on culture (seropositive group), or if AIDS developed according to the clinical criteria outlined above (AIDS group). Since AIDS developed in some of the HIV-1—infected children during the study period, fevers or cases of malaria in these children were analyzed according to their clinical HIV status (seropositive or AIDS group) at the time of each episode. Children born to seropositive mothers who had reverted to seronegativity at 12 or 18 months of age were defined as the group that reverted to seronegativity.26 Children born to seronegative mothers who remained seronegative through 18 months of age were defined as the seronegative group.
Outcome Variables and Statistical Analysis
The incidence of malaria was assessed by comparing fevers per child-year, cases of malaria per child-year, and rates of positivity of malaria smears (equivalent to the proportion of fevers diagnosed as malaria) among the groups of children. The severity of malaria was assessed by comparing the geometric mean density of parasites among the infected children and the rates per child-year of cases of malaria that resulted in hospitalization or death; the cause of each hospitalization and death was ascertained in routine evaluations and in separate studies of disease-specific morbidity and mortality.14 , 16 , 27 , 28 The response to antimalarial therapy was assessed by comparing rates of treatment failure, defined as the proportion of children treated with quinine who had positive smears for malaria 7 or 14 days after beginning therapy. The effect of P. falciparum infection on the progression of HIV-related disease was assessed by comparing the incidence of malaria in HIV-1—infected children in whom AIDS developed with the incidence in those in whom AIDS did not develop.
Chi-square and Fisher's exact tests were used to assess categorical associations, and two-tailed Student's independent t-tests were used to evaluate differences in the natural log of the geometric mean density of parasites. A P value of <0.05 was considered to indicate statistical significance.
Results
Outcomes and Duration of Follow-up
The cohort of 587 children was followed for 7126 child-months, or 593.8 child-years (Table 1Table 1
Outcome and Duration of Follow-up of Study Children, According to HIV Status, from August 1987 to August 1988.). Of the 76 children with HIV-1 infection in August 1987, 3 had AIDS, and AIDS had developed in 36 additional children by August 1988; a total of 39 children therefore had AIDS at some point during the study period. Nine children born to seropositive mothers died and one was lost to follow-up before they were found to be infected with HIV-1 or had reverted to seronegativity; these children were excluded from the groups with HIV-1 infection (the seropositive group and the AIDS group) and from the group that reverted to seronegativity because their HIV status was undetermined. The proportion of children with AIDS who died (44 percent) was significantly higher than that of seropositive children (16 percent), those who reverted to seronegativity (2 percent), or seronegative children (3 percent) (P = 0.02, <0.001, and <0.001, respectively). No children with AIDS or seropositive children, and only 2 percent of those in the group that reverted to seronegativity and the seronegative group, were lost to follow-up.Incidence of Malaria
Overall, 2899 episodes of fever were observed and evaluated with a smear for malaria (Table 2Table 2
Incidence of Malaria in Study Children According to HIV Status.*). All but 11 children had at least 1 episode of fever, and the highest number of episodes of fever per child was 18. The incidence of fever in the children with AIDS (8.2 fevers per child-year) was somewhat higher than in the seropositive children (6.0) (odds ratio = 1.4; 95 percent confidence interval, 0.7 to 2.6), and significantly higher than in the group that reverted to seronegativity (4.3) (odds ratio = 1.9; 95 percent confidence interval, 1.1 to 3.3) and the seronegative group (4.8) (odds ratio = 1.7; 95 percent confidence interval, 1.0 to 3.0).A total of 271 cases of P. falciparum malaria were identified in 173 children. The incidence of malaria in the children with AIDS (0.82 case of malaria per child-year) was higher, although not significantly so, than in the seropositive children (0.47 case; odds ratio = 1.7; 95 percent confidence interval, 0.7 to 4.5), those who reverted to seronegativity (0.52 case; odds ratio = 1.6; 95 percent confidence interval, 0.7 to 3.6), and the seronegative group (0.40 case; odds ratio = 2.1; 95 percent confidence interval, 0.9 to 4.6). No significant differences were found in the incidence of fever or malaria between the seropositive children and the children who reverted to seronegativity and the seronegative children. Importantly, the rates of positivity of the malaria smears were similar in all groups (range, 8.3 to 11.9 percent), and no significant differences were found.
Severity of Malaria
The geometric mean density of parasites was higher, although not significantly so, in the children with AIDS (11,257 parasites per microliter) than in the seropositive children (2394), the children who reverted to seronegativity (4328), and the seronegative children (3854) (P = 0.068, 0.097, and 0.065, respectively) (Table 3Table 3
Severity of Malaria in Study Children, According to HIV Status.*). No differences were found between seropositive children and those who reverted to seronegativity or those who were seronegative. All the mean densities of parasites were relatively low, however, and the differences between them were of little clinical importance. (A density of 10,000 parasites per microliter is equivalent to the infection of only 0.2 percent of a patient's erythrocytes, assuming a normal red-cell count; in contrast, hyperparasitemia, according to the WHO definition, constitutes a density of more than 250,000 parasites per microliter, or more than 5 percent of a patient's erythrocytes.29)The hospitalization of nine children (one with AIDS, three who reverted to seronegativity, and five who were seronegative) and the deaths of three (one with AIDS, one who was seronegative, and one of undetermined HIV status) were attributed to malaria. The rates per child-year of cases of malaria that resulted in hospitalization and death were slightly higher in the children with AIDS than in the other groups, but no significant differences were observed. Of the 23 deaths in children with HIV-1 infection (those who had AIDS or were seropositive), only 1 (4 percent) was attributed to malaria; the most frequent causes of death in these children were diarrhea (39 percent), pneumonia (35 percent), malnutrition (26 percent), measles (17 percent), and meningitis (13 percent).
Response to Antimalarial Therapy
A total of 198 children were enrolled in the malaria-therapy component of the study, of whom 149 (75 percent) returned on day 7 and 99 (50 percent) returned on day 14 for follow-up smears for malaria; no significant differences were observed in the rates of return on day 7 or day 14 among the various groups (Table 4Table 4
Response to Therapy of the 198 Study Children in the Malaria-Therapy Component, According to HIV Status.). Rates of return were less than 100 percent because some mothers were reluctant to return for follow-up when their children had become clinically well. None of the children who failed to return for a follow-up smear died. The rate of treatment failure in the children with AIDS was slightly higher than in the other groups, but the number of treatment failures was small and no significant differences were observed.Malaria and the Progression of HIV-Related Disease
Of the 73 children with HIV-1 infection who did not have AIDS in August 1987, AIDS developed in 36 during the 13-month study period. The incidence of malaria in these 36 children (before AIDS developed) was 5 cases per 15.2 child-years (0.33), lower (although not significantly so) than the incidence of 20 cases per 37.1 child-years (0.54) in the 37 children with HIV-1 infection in whom AIDS did not develop (odds ratio = 0.6; 95 percent confidence interval, 0.2 to 2.2; P = 0.6).
Discussion
In this study, no significant differences were found in the incidence, severity, or response to therapy of malaria between the children with progressive HIV-1 infection and the seronegative controls. A larger sample would have increased the power of this study to detect statistical differences among the four groups of children. However, the careful clinical monitoring of HIV-related symptoms, the extensive system of surveillance established to detect cases of malaria, and the extremely low number of children who were lost to follow-up add considerable strength to these findings.
The elevated incidence of malaria that was found in the children with AIDS can be explained in part by the significantly higher incidence of fever in this group. Since AIDS itself is associated with fever, the children with AIDS had more fevers and were consequently tested for malaria more frequently than the children in the other groups (hence, there was an ascertainment bias). Since the rates of positivity of the malaria smears were similar in all groups, it is reasonable to assume that at least some of the cases of malaria in the children with AIDS were attributable to the detection of incidental parasitemia in children with AIDS-related fever. Thus, the true incidence of malaria in the children with AIDS was probably similar to that observed in the other groups. Further studies of the background rates of positivity of malaria smears from nonfebrile children might help to clarify this issue.
Because of the high mortality rate among the children with AIDS (17 of 39 died during the study period), they were at risk for P. falciparum infection for only a limited period of time. As a result, the number of cases of malaria identified in this group was relatively small. Nevertheless, only 1 of the 17 deaths in children with AIDS was attributed to malaria; diarrhea, pneumonia, malnutrition, measles, and meningitis were identified as the primary causes of mortality in the children with HIV-1 infection in this cohort.14 , 27 , 28 Thus, although the high mortality rate in the children with AIDS may have reduced the statistical power of our study, it is crucial to note that malaria was responsible for only a small proportion of the deaths in this group.
Our efforts to provide optimal clinical care for the children enrolled in this study may have affected our ability to detect differences in some of the outcome variables. In Kinshasa, where the transmission of malaria is intense30 and the prevalence of chloroquine-resistant P. falciparum is high,31 alarming rates of malaria-related morbidity and mortality in infants have been reported.15 In this study, however, the intensive education of mothers to be vigilant for episodes of fever, coupled with the rapid administration of effective antimalarial therapy, was probably responsible for arresting many episodes of malaria early in the course of infection. As a result, the geometric mean densities of parasites, the number of hospitalizations for malaria, and the number of deaths from malaria were probably lower than might otherwise have been observed.
In addition, because P. falciparum infection is potentially life-threatening in children in Kinshasa, we selected an antimalarial regimen that had been shown to be highly effective in this setting.24 The number of treatment failures was consequently small, and the failures that did occur were probably caused by the improper administration of the quinine regimen rather than an inadequate host response to P. falciparum infection or insensitivity of the infecting parasites to quinine. Our findings regarding the incidence of malaria and the response to quinine therapy are consistent with those of a study of children recently infected with HIV-1 undertaken at Mama Yemo Hospital in 1986.32
Finally, no significant difference in the incidence of malaria was found between children with HIV-1 infection in whom AIDS developed and those in whom it did not. This finding must be interpreted with caution because of the small number of cases of malaria that were identified in children with HIV-1 infection, the relatively short period of follow-up, and the absence of any laboratory data with which to control for the underlying immunologic status of the children. Nevertheless, no evidence was found to suggest that malaria has any role in accelerating the rate of progression of HIV-1 disease.
This investigation demonstrates that HIV-1 and P. falciparum malaria continue to pose serious threats to the health of children in Kinshasa. Our data indicate, however, that there is no adverse clinical or epidemiologic association between these two important public health problems.
We are indebted to Dr. Phuc Nguyen-Dinh, Dr. Nsanga Badi, Ms. Jacquelin Roberts, and Ms. Michele Zweig for guidance and assistance; to Citizens Mosengo Mputu and Lobengo Bokito for clinical assistance; to Drs. Carlos Campbell, William Heyward, Pauline Thomas, and Martha Rogers for editorial assistance; and to Dr. James Curran for his support.
Source Information
From the Malaria Branch, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta (A.E.G.); Projet SIDA, Kinshasa, Zaire (W.N., R.W.R., M.M., M.N., N.K., M.B., N.M., S.E.H.); the Division of HIV/AIDS, Center for Infectious Diseases, Centers for Disease Control, Atlanta (R.W.R.); and the Department of Pediatrics, Mama Yemo Hospital, Kinshasa, Zaire (F.D.). Address reprint requests to Dr. Greenberg at the Division of HIV/AIDS, Mailstop E-45, CDC, Atlanta, GA 30333.
- References
References
1
Smith
CrossRef | Web of Science | Medline2
Morrow
CrossRef | Web of Science | Medline3
Ho
CrossRef | Web of Science | Medline4
Troye-Blomberg M, Perlmann P. T cell functions in Plasmodium falciparum and other malarias. In: Perlmann P, Wigzell H, eds. Malaria immunology. Vol. 41 of Progress in allergy. Basel, Switzerland: Karger, 1988:253–87.
5
Margolick
Web of Science | Medline6
Nguyen-Dinh
Web of Science | Medline7
Nguyen-Dinh P, Greenberg AE, Ryder RW, et al. Absence of association between HIV seropositivity and Plasmodium falciparum malaria in Kinshasa, Zaire. Presented at the Third International Conference on AIDS, Washington, D.C., June 1–5, 1987. abstract.
8
Nguyen-Dinh P, Greenberg AE, Colebunders RL, Schable CA, Sulzer AJ, Bila K. HIV infection, AIDS, and Plasmodium falciparum malaria in an adult emergency ward population in Kinshasa, Zaire. Presented at the 36th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Los Angeles, California, November 29—December 3, 1987. abstract.
9
Greenberg
CrossRef | Web of Science | Medline10
Shaffer
CrossRef | Web of Science | Medline11
Simooya
CrossRef | Web of Science | Medline12
Mertens
CrossRef | Web of Science | Medline13
Goodgame
Full Text | Web of Science | Medline14
Ryder
Full Text | Web of Science | Medline15
Greenberg
Web of Science | Medline16
Nsa W, Manzila T, Mvula M, Matela B, Hassig S, Ryder R. Cause-specific morbidity in the first 18 months of life in 477 infants born to seropositive mothers in Zaire. In: Proceedings of the Fifth International Conference on AIDS, Montreal, June 4–9, 1989. Ottawa, Ont.: International Development Research Centre. 1989. abstract.
17
Acquired immunodeficiency syndrome (AIDS): WHO/CDC case definition for AIDS. Weekly Epidemiological Record. Vol. 61. No. 10. Geneva: World Health Organization, 1986:69–73.
18
Colebunders
Web of Science | Medline19
Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome . MMWR 1987; 36:Suppl 1S:1S–15S.
Medline20
Interpretation and use of the Western blot assay for serodiagnosis of human immunodeficiency virus type 1 infections . MMWR 1989; 38(S-7):1–7.
21
Feorino
CrossRef | Web of Science | Medline22
McGregor
CrossRef | Web of Science | Medline23
Sulzer 24
Greenberg
Web of Science | Medline25
Nguyen-Dinh
Web of Science | Medline26
Rogers
Full Text | Web of Science | Medline27
Nsa W, Ryder R, Baende E, et al. Mortality from perinatally-acquired HIV infection in African children. Presented at the Fourth International Conference on AIDS, Stockholm, Sweden, June 12–16, 1988. abstract.
28
Badi N, Ryder R, Nsuami M, Matela B, Nsa W. High HIV-associated infant mortality correlates with poor post-partum maternal health: 18 months follow-up of 477 children born to HIV + mothers in Zaire. Presented at the Fifth International Conference on AIDS, Montreal, June 4–9, 1989. abstract.
29
World Health Organization Malaria Action Programme
CrossRef | Web of Science | MedlineErratum, Trans R Soc Trop Med Hyg 1986; 80:571.
CrossRef30
Ngimbi
Medline31
Nguyen-Dinh
Web of Science | Medline32
Colebunders
CrossRef | Web of Science | Medline
- Citing Articles (37)
Citing Articles
1
Sascha R Ellington, Caroline C King, Athena P Kourtis. (2011) Host factors that influence mother-to-child transmission of HIV-1: genetics, coinfections, behavior and nutrition. Future Virology 6:12, 1451-1469
CrossRef2
Clara Flateau, Guillaume Le Loup, Gilles Pialoux. (2011) Consequences of HIV infection on malaria and therapeutic implications: a systematic review. The Lancet Infectious Diseases 11:7, 541-556
CrossRef3
Jane Achan, Ambrose O Talisuna, Annette Erhart, Adoke Yeka, James K Tibenderana, Frederick N Baliraine, Philip J Rosenthal, Umberto D'Alessandro. (2011) Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malaria Journal 10:1, 144
CrossRef4
Athena P. Kourtis, Marc Bulterys. (2010) Mother-to-Child Transmission of HIV: Pathogenesis, Mechanisms and Pathways. Clinics in Perinatology 37:4, 721-737
CrossRef5
Gregory C. Davenport, Collins Ouma, James B. Hittner, Tom Were, Yamo Ouma, John M. Ong'echa, Douglas J. Perkins. (2010) Hematological predictors of increased severe anemia in Kenyan children coinfected with Plasmodium falciparum and HIV-1. American Journal of Hematology 85:4, 227-233
CrossRef6
Nereide Stela Santos-Magalhães, Vanessa Carla Furtado Mosqueira. (2010) Nanotechnology applied to the treatment of malaria. Advanced Drug Delivery Reviews 62:4-5, 560-575
CrossRef7
Mohamed Houseni, Wichana Chamroonrat, Sabah Servaes, Abass Alavi, Hongming Zhuang. (2008) Applications of PET/CT in Pediatric Patients with Fever of Unknown Origin. PET Clinics 3:4, 605-619
CrossRef8
Job CJ Calis, Michaël Boele van Hensbroek, Rob J de Haan, Peter Moons, Bernard J Brabin, Imelda Bates. (2008) HIV-associated anemia in children: a systematic review from a global perspective. AIDS 22:10, 1099-1112
CrossRef9
Sibyl Geelen, Philippa Musoke. 2008. Antiretroviral Treatment and Follow-up of HIV-infected Children in Resource-limited Settings. , 621-635.
CrossRef10
Feiko O. ter Kuile, James A.G. Whitworth. 2008. Malaria and HIV Infection. , 747-753.
CrossRef11
Lisa M Bebell, Anne Gasasira, Moses Kiggundu, Christian Dokomajilar, Moses R Kamya, Edwin D Charlebois, Diane Havlir, Philip J Rosenthal, Grant Dorsey. (2007) HIV-1 Infection in Patients Referred for Malaria Blood Smears at Government Health Clinics in Uganda. JAIDS Journal of Acquired Immune Deficiency Syndromes 46:5, 624-630
CrossRef12
R.C. Vickery, Daniel L. Klayman. 2007. Malaria. .
CrossRef13
Miriam K. Laufer, Christopher V. Plowe. (2007) The interaction between HIV and malaria in Africa. Current Infectious Disease Reports 9:1, 47-54
CrossRef14
Kirsten Hewitt, Richard Steketee, Victor Mwapasa, Jimmy Whitworth, Neil French. (2006) Interactions between HIV and malaria in non-pregnant adults: evidence and implications. AIDS 20:16, 1993-2004
CrossRef15
L. RENIA, S. M. POTTER. (2006) Co-infection of malaria with HIV: an immunological perspective. Parasite Immunology 0:0, 060706013007005-???
CrossRef16
Richard O Otieno, Collins Ouma, John M Ongʼecha, Christopher C Keller, Tom Were, Eliud N Waindi, Marian G Michaels, Richard D Day, John M Vulule, Douglas J Perkins. (2006) Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria. AIDS 20:2, 275-280
CrossRef17
D. R. Snydman, M. Walker, J. G. Kublin, J. R. Zunt. (2006) Parasitic Central Nervous System Infections in Immunocompromised Hosts: Malaria, Microsporidiosis, Leishmaniasis, and African Trypanosomiasis. Clinical Infectious Diseases 42:1, 115-125
CrossRef18
C. Cohen, A. Karstaedt, J. Frean, J. Thomas, N. Govender, E. Prentice, L. Dini, J. Galpin, H. Crewe-Brown. (2005) Increased Prevalence of Severe Malaria in HIV-Infected Adults in South Africa. Clinical Infectious Diseases 41:11, 1631-1637
CrossRef19
M. H. Craig, I. Kleinschmidt, D. Le Sueur, B. L. Sharp. (2004) Exploring 30 years of malaria case data in KwaZulu-Natal, South Africa: Part II. The impact of non-climatic factors. Tropical Medicine and International Health 9:12, 1258-1266
CrossRef20
Eduardo Villamor, Maulidi R. Fataki, Roger L. Mbise, Wafaie W. Fawzi. (2003) Malaria parasitaemia in relation to HIV status and vitamin A supplementation among pre-school children. Tropical Medicine and International Health 8:12, 1051-1061
CrossRef21
Sarah L. Rowland-Jones, Barbara Lohman. (2002) Interactions between malaria and HIV infection—an emerging public health problem?. Microbes and Infection 4:12, 1265-1270
CrossRef22
Michael F. Good. (2001) TOWARDS A BLOOD-STAGE VACCINE FOR MALARIA: ARE WE FOLLOWING ALL THE LEADS?. Nature Reviews Immunology 1:2, 117-125
CrossRef23
Neil French, Jessica Nakiyingi, Eric Lugada, Christine Watera, James A. G. Whitworth, Charles F. Gilks. (2001) Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS 15:7, 899-906
CrossRef24
D. L. Palmer, P. R. Mason, C. Pasi, O. Tobiwa. (2000) Value of Mandatory Testing for Human Immunodeficiency Virus in a Sub-Saharan Hospital Population. Clinical Infectious Diseases 31:5, 1258-1265
CrossRef25
James Whitworth, Dilys Morgan, Maria Quigley, Adrian Smith, Billy Mayanja, Henry Eotu, Nicholas Omoding, Martin Okongo, Samuel Malamba, Amato Ojwiya. (2000) Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. The Lancet 356:9235, 1051-1056
CrossRef26
Neil French, Charles F. Gilks. (2000) Fresh from the field: some controversies in tropical medicine and hygiene. Transactions of the Royal Society of Tropical Medicine and Hygiene 94:3, 233-237
CrossRef27
Godfrey Biemba, Dennis Dolmans, Philip E. Thuma, Gunter Weiss, Victor R. Gordeuk. (2000) Severe anaemia in Zambian children with Plasmodium falciparum malaria. Tropical Medicine and International Health 5:1, 9-16
CrossRef28
Irving F. Hoffman, Charles S. Jere, Terrie E. Taylor, Peter Munthali, John R. Dyer, Jack J. Wirima, Stephen J. Rogerson, Newton Kumwenda, Joe J. Eron, Susan A. Fiscus, Hrishitesh Chakraborty, Taha E. Taha, Myron S. Cohen, Malcolm E. Molyneux. (1999) The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration. Aids 13:4, 487-494
CrossRef29
Francine H. Verhoeff, Bernard J. Brabin, C. Anthony Hart, Lyson Chimsuku, Peter Kazembe, Robin L. Broadhead. (1999) Increased prevalence of malaria in HIV-infected pregnant women and its implications for malaria control. Tropical Medicine and International Health 4:1, 5-12
CrossRef30
Vinetz, Joseph M., Li, Jun, McCutchan, Thomas F., Kaslow, David C., . (1998) Plasmodium malariae Infection in an Asymptomatic 74-Year-Old Greek Woman with Splenomegaly. New England Journal of Medicine 338:6, 367-371
Full Text31
Alfons Gompel, Phyllis Kozarsky, Robert Colebunders. (1997) Adult Travelers with HIV Infection. Journal of Travel Medicine 4:3, 136-143
CrossRef32
ISRAEL KALYESUBULA, PHILIPPA MUSOKE-MUDIDO, LAWRENCE MARUM, DANSTAN BAGENDA, ESTHER ACENG, CHRISTOPHER NDUGWA, KAREN OLNESS. (1997) Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children. The Pediatric Infectious Disease Journal 16:9, 876-881
CrossRef33
Alain Blanchard, Luc Montagnier, Marie-Lise Gougeon. (1997) Influence of microbial infections on the progression of HIV disease. Trends in Microbiology 5:8, 326-331
CrossRef34
Gijs Walraven, Angus Nicoll, Mathew Njau, Ian Timaeus. (1996) The impact of HIV-1 infection on child health in sub-Saharan Africa: the burden on the health services. Tropical Medicine & International Health 1:1, 3-14
CrossRef35
Honore A. Meda, Felix Doua, Claude Laveissière, Tanoh W. Miezan, Els Gaens, Kari Brattegaard, Aimé de Muynck, Kevin M. De Cock. (1995) Human immunodeficiency virus infection and human African trypanosomiasis: a case-control study in Côte d'Ivoire. Transactions of the Royal Society of Tropical Medicine and Hygiene 89:6, 639-643
CrossRef36
Taha E.T. Taha, Joseph K. Canner, Gina A. Dallabetta, John D. Chiphangwi, George Liomba, Anne Marie Wangel, Alfred J. Saah, Paolo G. Miotti. (1994) Childhood malaria parasitaemia and human immunodeficiency virus infection in Malawi. Transactions of the Royal Society of Tropical Medicine and Hygiene 88:2, 164-165
CrossRef37
A. Zumla, S. L. Croft. (1992) Chemotherapy and immunity in opportunistic parasitic infections in AIDS. Parasitology 105:S1, S93
CrossRef
