Coinfection with HIV and Tropical Infectious Diseases. I. Protozoal Pathogens
TL;DR: An overview of the available data on the interactions between HIV and tropical pathogens is presented, and Tropical protozoa are discussed here; other tropical pathogens are discussed in a related mini-review in this issue of Clinical Infectious Diseases.
Abstract: The brunt of the human immunodeficiency virus (HIV) pandemic has been borne disproportionately by resource-poor regions of the world, where tropical infectious diseases continue to hold greatest sway. As a result, our understanding of the epidemiological, biological, and clinical interactions between HIV and tropical pathogens has lagged, compared with our understanding of the interactions between HIV and pathogens that are common in the industrialized world. Because of the current rapid expansion of HIV care in the tropics, with increasing resources being made available, an overview of the available data is timely. Tropical protozoa are discussed here; other tropical pathogens are discussed in a related mini-review in this issue of Clinical Infectious Diseases.
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TL;DR: Several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in high-burden countries are described.
Abstract: Summary: With an estimated 9.4 million new cases globally, tuberculosis (TB) continues to be a major public health concern. Eighty percent of all cases worldwide occur in 22 high-burden, mainly resource-poor settings. This devastating impact of tuberculosis on vulnerable populations is also driven by its deadly synergy with HIV. Therefore, building capacity and enhancing universal access to rapid and accurate laboratory diagnostics are necessary to control TB and HIV-TB coinfections in resource-limited countries. The present review describes several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in such countries. Recently, the WHO has endorsed some of these novel methods, and they have been made available at discounted prices for procurement by the public health sector of high-burden countries. In addition, international and national laboratory partners and donors are currently evaluating other new diagnostics that will allow further and more rapid testing in point-of-care settings. While some techniques are simple, others have complex requirements, and therefore, it is important to carefully determine how to link these new tests and incorporate them within a country's national diagnostic algorithm. Finally, the successful implementation of these methods is dependent on key partnerships in the international laboratory community and ensuring that adequate quality assurance programs are inherent in each country's laboratory network.
457 citations
TL;DR: This review concludes that routine monitoring on ART for HIV‐infected patients and individuals transferring care from a different HIV healthcare setting is a viable option and should be considered.
Abstract: Table of Contents
1. Levels of evidence
1.1 Reference
2. Introduction
3. Auditable targets
4. Table summaries
4.1 Initial diagnosis
4.2 Assessment of ART-naive individuals
4.3 ART initiation
4.4 Initial assessment following commencement of ART
4.5 Routine monitoring on ART
4.6 References
5. Newly diagnosed and transferring HIV-positive individuals
5.1 Initial HIV-1 diagnosis
5.2 Tests to determine whether acquisition of HIV infection is recent
5.3 Individuals transferring care from a different HIV healthcare setting
5.4 Communication with general practitioners and shared care
5.5 Recommendations
5.6 References
6. Patient history
6.1 Initial HIV-1 diagnosis
6.2 Monitoring of ART-naive patients
6.3 Pre-ART initiation assessment
6.4 Monitoring individuals established on ART
6.5 Assessment of adherence
6.6 Recommendations
6.7 References
7. Examination
7.1 Recommendations
8. Identifying the need for psychological support
8.1 References
9. Assessment of immune status
9.1 CD4 T cell counts
9.2 CD4 T cell percentage
9.3 References
10. HIV viral load
10.1 Initial diagnosis/ART naive
10.2 Post ART initiation
10.3 Individuals established on ART
10.4 Recommendations
10.5 References
11. Technical aspects of viral load testing
11.1 References
12. Viral load kinetics during ART and viral load ‘blips’
12.1 References
13. Proviral DNA load
13.1 References
14. Resistance testing
14.1 Initial HIV-1 diagnosis
14.2 ART-naive
14.3 Post treatment initiation
14.4 ART-experienced
14.5 References
15. Subtype determination
15.1 Disease progression
15.2 Transmission
15.3 Performance of molecular diagnostic assays
15.4 Response to therapy
15.5 Development of drug resistance
15.6 References
16. Other tests to guide use of specific antiretroviral agents
16.1 Tropism testing
16.2 HLA B*5701 testing
16.3 References
17. Therapeutic drug monitoring
17.1 Recommendations
17.2 References
18. Biochemistry testing
18.1 Introduction
18.2 Liver function
18.3 Renal function
18.4 Dyslipidaemia in HIV-infected individuals
18.5 Other biomarkers
18.6 Bone disease in HIV-infected patients
18.7 References
19. Haematology
19.1 Haematological assessment and monitoring
19.2 Recommendations
19.3 References
20. Serology
20.1 Overview
20.2 Hepatitis viruses
20.3 Herpes viruses
20.4 Measles and rubella
20.5 Cytomegalovirus (CMV)
20.6 References
21. Other microbiological screening
21.1 Tuberculosis screening
21.2 Toxoplasma serology
21.3 Tropical screening
21.4 References
22. Sexual health screening including anal and cervical cytology
22.1 Sexual history taking, counselling and sexually transmitted infection (STI) screening
22.2 Cervical and anal cytology
22.3 Recommendations
22.4 References
23. Routine monitoring recommended for specific patient groups
23.1 Women
23.2 Older age
23.3 Injecting drug users
23.4 Individuals coinfected with HBV and HCV
23.5 Late presenters
23.6 References
Appendix
205 citations
TL;DR: This review covers epidemiology, phylogeny, diagnostics and treatment of human babesiosis and the potential risk of transfusion-transmitted disease with a special focus on the European situation.
Abstract: Although best known as an animal disease, human babesiosis is attracting increasing attention as a worldwide emerging zoonosis. Humans are commonly infected by the bite of ixodid ticks. Rare ways of transmission are transplacental, perinatal and transfusion-associated. Infection of the human host can cause a very severe host-mediated pathology including fever, and hemolysis leading to anemia, hyperbilirubinuria, hemoglobinuria and possible organ failure. In recent years, apparently owing to increased medical awareness and better diagnostic methods, the number of reported cases in humans is rising steadily worldwide. Hitherto unknown zoonotic Babesia spp. are now being reported from geographic areas where babesiosis was not previously known to occur and the growing numbers of travelers and immunocompromised individuals suggest that the frequency of cases in Europe will also continue to rise. Our review is intended to provide clinicians with practical information on the clinical management of this rare, but potentially life-threatening zoonotic disease. It covers epidemiology, phylogeny, diagnostics and treatment of human babesiosis and the potential risk of transfusion-transmitted disease with a special focus on the European situation.
149 citations
TL;DR: This review presents, analyzes and provides significant insights and recent advances about the promising biomedical applications of nanoparticles including bioimaging of biological environments and its role as a significant tool for early detection of many diseases with respect to traditional means.
139 citations
TL;DR: An overview of the available data on tropical helminths, fungi, bacteria, and viruses is provided here; interactions between HIV and tropical protozoa are covered in a related mini-review in this issue of Clinical Infectious Diseases.
Abstract: The morbidity, mortality, and social disruption caused by the human immunodeficiency virus (HIV) pandemic continue to weigh disproportionately on resource-poor regions of the tropics. As a result, the potential for significant epidemiological, biological, and clinical interactions between HIV and other tropical pathogens is great. An overview of the available data on tropical helminths, fungi, bacteria, and viruses is provided here; interactions between HIV and tropical protozoa are covered in a related mini-review in this issue of Clinical Infectious Diseases. Special attention is given to evidence relevant to the hypothesis that helminth coinfection plays a particularly important role in accelerating the pace of HIV pathogenesis in the tropics.
125 citations
References
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TL;DR: HIV-1 infection is associated with an increased frequency of clinical malaria and parasitaemia, and this association tends to become more pronounced with advancing immunosuppression, and could have important public-health implications for sub-Saharan Africa.
476 citations
TL;DR: In this paper, the authors reviewed available information collected since the first report 15 years ago that HIV impaired the ability of pregnant women to control malaria parasitemia and found that pregnant women experienced consistently more peripheral and placental malaria (summary relative risk = 1.58 and 1.66, respectively), higher parasite densities, and more febrile illnesses, severe anemia, and adverse birth outcomes than HIV-uninfected women, particularly in multigravidae.
Abstract: In sub-Saharan Africa, human immunodeficiency virus (HIV) and malaria are among the leading causes of morbidity during pregnancy. We reviewed available information collected since the first report 15 years ago that HIV impaired the ability of pregnant women to control malaria parasitemia. Results from 11 studies showed that HIV-infected women experienced consistently more peripheral and placental malaria (summary relative risk = 1.58 and 1.66, respectively), higher parasite densities, and more febrile illnesses, severe anemia, and adverse birth outcomes than HIV-uninfected women, particularly in multigravidae. Thus, HIV alters the typical gravidity-specific pattern of malaria risk by shifting the burden from primarily primigravidae and secundigravidae to all pregnant women. The proportional increase of malaria during pregnancy attributable to HIV was estimated to be 5.5% and 18.8% for populations with HIV prevalences of 10% and 40%, respectively. Maternal malaria was associated with a two-fold higher HIV-1 viral concentrations. Three studies investigating whether placental malaria increased mother-to-child HIV-1 transmission showed conflicting results, possibly reflecting a complex balance between placental malarial immune responses and stimulation of HIV-1 viral replication. Further investigations of interactions between antiretroviral drugs, prophylaxis with cotrimoxazole, and antimalarial drugs in pregnant women are urgently needed. Although much has been learned in the past 15 years about the interaction between malaria and HIV-1 during pregnancy, many issues still require further information to improve our understanding. There is a clear need to strengthen the deployment of existing malaria and HIV prevention and intervention measures for pregnant women.
348 citations
TL;DR: It is suggested that an increase in the proportion of cases with more fatal manifestations of severe malaria is likely to occur only after transmission has been reduced to low levels where the overall incidence islikely to be low.
Abstract: ContextThere are concerns that malaria control measures such as use of insecticide-treated
bed nets, by delaying acquisition of immunity, might result in an increase
in the more severe manifestations of malaria. An understanding of the relationships
among the level of exposure to Plasmodium falciparum,
age, and severity of malaria can provide evidence of whether this is likely.ObjectiveTo describe the clinical manifestations and case fatality of severe P falciparum malaria at varying altitudes resulting in
varying levels of transmission.Design, Setting, and PatientsA total of 1984 patients admitted for severe malaria to 10 hospitals
serving populations living at levels of transmission varying from very low
(altitude >1200 m) to very high (altitude <600 m) in a defined area of
northeastern Tanzania, studied prospectively from February 2002 to February
2003. Data were analyzed in a logistic regression model and adjusted for potential
clustering within hospitals.Main Outcome MeasuresSpecific syndromes of severe malaria; mortality.ResultsThe median age of patients was 1 year in high transmission, 3 years
in moderate transmission, and 5 years in low transmission areas. The odds
of severe malarial anemia (hemoglobin <5 g/dL) peaked at 1 year of age
at high transmission and at 2 years at moderate and low transmission intensities
and then decreased with increasing age (P = .002).
Odds were highest in infants (0-1 year: referent; 2-4 years: odds ratio [OR],
0.83; 95% confidence interval [CI], 0.72-0.96), 5 to <15 years: OR, 0.44;
95% CI, 0.27-0.72; ≥15 years: OR, 0.44; 95% CI, 0.27-0.73; P<.001) and high transmission intensity areas (altitude <600
m: referent; 600 m to 1200 m: OR, 0.55; 95% CI, 0.35-0.84; >1200 m: OR, 0.55;
95% CI, 0.26-1.15; P for trend = .03).
The odds of cerebral malaria were significantly higher in low transmission
intensity areas (altitude of residence <600 m: referent; 600 m to 1200
m: OR, 3.17; 95% CI, 1.32-7.60; >1200 m: OR, 3.76; 95% CI, 1.96-7.18; P for trend = .003) and with age 5 years and
older (0-1 year: referent; 2-4 years: OR, 1.57; 95% CI, 0.82-2.99; 5 to <15
years: OR, 6.07; 95% CI, 2.98-12.38; ≥15 years: OR, 6.24; 95% CI, 3.47-11.21; P<.001). The overall case-fatality rate of 7% (139 deaths)
was similar at high and moderate levels of transmission but increased to 13%
in low transmission areas (P = .03), an
increase explained by the increase in the proportion of cases with cerebral
malaria.ConclusionsAge and level of exposure independently influence the clinical presentation
of severe malaria. Our study suggests that an increase in the proportion of
cases with more fatal manifestations of severe malaria is likely to occur
only after transmission has been reduced to low levels where the overall incidence
is likely to be low.
300 citations
TL;DR: The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. Falconerum on fetal growth and infant survival.
Abstract: In Africa, the human immunodeficiency virus (HIV) is the most serious emerging infection and Plasmodium falciparum malaria is one of the most prevalent infectious diseases. Both infections have serious consequences in pregnant women, their fetuses, and infants. We examined the association between HIV and P. falciparum in pregnant women enrolled in a malaria chemoprophylaxis study in rural Malawi. Pregnant women (n = 2,946) were enrolled at their first antenatal clinic visit (mean 5.6 months of pregnancy), placed on one of three chloroquine regimens, and followed through delivery. Plasmodium falciparum parasitemia was measured at enrollment, monthly thereafter, at delivery, and 2-6 months postpartum; placental and newborn (umbilical cord blood) infection was measured for hospital-delivered infants. Serum collected during pregnancy was tested for antibodies to HIV by enzyme-linked immunoassay with Western blot confirmation. Parasitemia was detected in 46% of 2,946 women at enrollment and 19.1% at delivery; HIV seroprevalence was 5.5%. The prevalence and geometric mean density (GMPD) of parasitemia at enrollment and at delivery were higher in HIV-seropositive(+) than in HIV-seronegative(-) women (at enrollment: 57% prevalence and a GMPD of 1,558 parasites/mm3 versus 44% and 670/mm3, respectively; P < 0.0001; and at delivery: 35% and 1,589/mm3 versus 18% and 373/mm3; P < 0.0005). Placental infection rates were higher in HIV(+) compared with HIV(-) women, (38% versus 23%; P < 0.0005). This association was strongest in multigravidas. Compared with infants born to HIV(-) women, newborns born to HIV(+) women had higher rates of umbilical cord blood parasitemia. Both HIV(+) and HIV(-) women had similar rates of parasitemia 2-6 months postpartum. The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. falciparum on fetal growth and infant survival.
273 citations
TL;DR: Data support an interaction between symptomatic P. falciparum and HIV, and suggest an additional HIV-related public health problem in Africa.
Abstract: BACKGROUND: Falciparum malaria and HIV-1 infection are two of the most important health problems facing sub-Saharan Africa. No convincing evidence of an association between symptomatic malaria and HIV-1 infection has been found. OBJECTIVE: To investigate the effect of HIV-associated immunosuppression on malarial fever rates. DESIGN: An observational cohort study in HIV-specific, primary healthcare clinics in Entebbe, Uganda, on 1371 HIV-1-infected adults participating in a randomized trial of 23-valent pneumococcal vaccine. METHODS: Cohort members underwent routine 6 monthly surveillance and had open clinic access when sick. Episodes of fever were assessed according to standardized protocols. Rates of malaria are described according to HIV immune status determined by CD4 T cell counts. RESULTS: Incidence rates of Plasmodium falciparum malarial fever showed a marked inverse relationship with CD4 T cell count; 140, 93 and 57 cases per 1000 pyo for CD4 T cell groups 500 respectively, P < 0.001. Malarial fever definitions incorporating parasite density criteria (derived from asymptomatic surveillance) to correct for chance findings of fever and P. falciparum parasitaemia, did not affect the association of incidence rates with immunosuppression. CONCLUSION: These data support an interaction between symptomatic P. falciparum and HIV. Emphasis on mosquito avoidance measures should be an important component of education and counselling of HIV/AIDS patients in malaria-endemic areas, and suggests an additional HIV-related public health problem in Africa.
245 citations