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Clinical and Epidemiological Analysis for HIV-exposed Infants in a Low Resource Setting: Evidence-based of PMTCT Interventions

Forschungsarbeit 2011 23 Seiten

Gesundheit - Public Health

Leseprobe

TABLE OF CONTENT

Abbreviations

Introduction
a. Definitions
b. Background
c. General objectives

1. Assessing abnormality of HIV infection in Neonates
1.1 Disease natural history
1.2. Chain of infection
1.3. Mode of transmission

2. Evidence based of PMTCT
2.1. Material and methodology
2.2. Diagnosis of HIV in infants
2.2.1 Statistical testing: sensitivity and specificity
2.2.2. Predictive values
2.3. Risk
2.3.1. Measures of relative risk
2.3.2. Odds ratio
2.3.3. Confidence interval
2.4. Prognosis
2.5. Treatments

3. Discussion

4. Conclusions

5. References

Annexes

ABBREVIATIONS

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Introduction

a. Definitions:

Clinical epidemiology is a fundamental epidemiologic approach based on the application of epidemiologic principles and methods in clinical setting. It’s a basic science of medicine (Bonita R, Beaglehole R, Kjellestrom, 2008).Its approach considers using epidemiologic principles and methods to make clinical decisions and to measure outcome of disease.[3]

Mostly, clinicians deal with individuals whilst epidemiologists deal with communities. Thus, the concept of clinical epidemiology seems to be contradictory with its application. However, the current increase of knowledge in clinical medicine and pharmacology, the curiosity of knowing the validity of laboratory tests, the quest of a final and correct diagnosis and the necessity of cost-effective and efficient therapies, made the role of epidemiology more and more imperative. In this era called ’’pharmacoepidemiology’’, researchers focus on the advantages and disadvantage of drugs, hence their effects. This let Kenneth Rothman, 2002 to say: ‘’outcomes research marries epidemiologic methods with clinical decision theory to determine which therapeutic approaches are the most cost-effective’’. [10]

This approach has lead to the concept of evidence –based medicine where sufficient proof are available to support a medical theory in disease management and promotion of various guidelines useful in clinical setting.Nonetheless, more medical and non medical conditions are still undiagnosed, under- diagnosed or wrongly diagnosed. As a consequence, extra, less cost-effective and unnecessary treatments are being prescribed. In this scenario, would the key to evidence- based medicine lie on diagnosis processes which are opaque to quantification and analysis, or on the deep-rooted knowledge of disease natural history, its transmission chain and physiopathology, or on the accuracy of diagnostic tests which have different level of interpretations according to their sensitivity or specificity? Or on prevention inputs to control the disease outcomes? These bottlenecks are generally and globally faced by clinicians whereas apply epidemiologic principles and fundamentals to research in clinical setting. This is not a question of controversy; Once understood and correctly applied, epidemiologic methods will raise a flow of evidences to audit the daily practice and make clinical decisions to amend or support existing therapeutic or management theories based on the findings.Again, implementation of new evidence-based innovations should be tested and completed.Recently, as discussing global health issues, Madon T et al ,2007 expressed concerns over most of discovered evidence-based theories that are not consistently tested or completed. [12]

In this research work, basic epidemiology principles and methods are applied to study the implication of PMTCT (Protection of Mother to Child Transmission of HIV) interventions in neonate populations born from HIV positive mothers in a low resource setting in Zambia.

b.Background:

In Zambia, roughly 80,000 infants are born annually from HIV infected mothers and are at risk of contracting the disease. An average of 20,000 are born with HIV each year (40%).The rate of vertical transmission varies from 15-25% in non-breastfeeding infants and double in breastfeeding ones. (Ministry of Health, National Protocol Guidelines, 2010). [14]

Over 9.2million children aged<5 years die every year in developing countries. (Murray CJL et all, 2003). [15] Almost 37 % of under-5 population deaths are neonatal causes with 28% due to preterm births. African regions are most affected in the world(WHO, world health Report,2005) [23].This data shows that strengthening PMTCT interventions and other preventive measures will have a major impact in reducing infant mortality and improve child survival rate.

Figure1: Causes of death in Children under-5, 2000-2003

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c.General objectives

The general objectives of this research paper won’t be nothing else than the application of epidemiologic principles and methods to the study of HIV in neonate’s population and the prevention measures. In clinical epidemiology the following outlines will be developed: from the assessment of abnormality in the general population (here the HIV-exposed neonates and infants), through the natural history, chain and mode of transmission, to the measurement of risk, treatment and prevention, a comprehensive descriptive and analytical review of PMTCT interventions and clinical presentations of HIV in this special population will be displayed to validate the daily evidence- based practices in low income countries with limited resources.

1. Assessing abnormality of HIV infection in Neonates

In this section, I display the context of disease abnormality in relation with HIV infection in a special population: ‘the neonates’’.

1.1. Disease natural history

Disease natural history refers to the progression of a particular disease over time in the human body in the absence of interventions. The ultimate outcome will be recovery, disability or death. The process starts with exposure then accumulations of factors that lead to the disease manifestations and progress. Each disease has got its natural history characteristics.However; there are common steps in the development.

The next graph shows the common steps of disease natural history.

Figure 2: Natural history of disease. (CDC, 2005) [4].

Exposure Pathological changes onset of symptoms diagnosis

Step of susceptibility Step of subclinical disease Step of clinical disease Step of recovery, disability or death.

The step of subclinical disease varies from seconds (e.g. anaphylactic shock) to months (e.g. hepatitis) and decade in some diseases (e.g.cancer, HIV/AIDS).This period is called incubation period for acute infections or latent phase in chronic diseases. Although symptoms and signs of disease are unapparent during this period, more diseases can be detected whether by some laboratory investigations, radiology procedures or screening tests. It’s very important to understand that screening tests should have high sensitivity and specificity to classify who has the disease and who does not among the population exposed. The advantage is that the earlier the diagnosis, the better the outcome (see chapter 2). The onset of symptoms marks the beginning of clinical stage. Most diagnosis are made during this period. Three terms are used to describe the disease progression along with the natural history of disease.

-Infectivity: This is the fraction of exposed people who become infected.
-Pathogenicity: this is the fraction of infected people who develop the clinical disease.
-Virulence: the fraction of people with clinical disease who develop a severe illness and may die.

Some diseases have high infectivity or pathogenicity or virulence than others.

For instance, HIV has a high infectivity, pathogenicity and virulence in neonates population. Around 30-40% of HIV exposed babies will contract the disease and half of them (50%) will die before their second birthday in absence of interventions (Newell ML et all, 2004). [17]

The natural history of HIV in neonates’ population is basically following the same steps as mentioned above. The exposed period which happens in utero (5 % infections), perinatally (10-20% infections) and during breastfeeding (10-20% infections); the subclinical stage (called asymptomatic); the clinical stage (symptomatic disease, classified by WHO from mild to severe form of the disease) and the last stage which is survival or death. The immunity response which is still naive and immature, make the complexity of diagnosis and clinical futures of HIV in early life. The absolute number of CD4 cells (target cells for HIV) is normally high in neonates and can mislead the clinician. However a clinical approach for early diagnosis using clinical WHO classification or IMCI algorithm have been develop and some threshold immunity values for early treatment as well (Mark W,2010).[13]

1.2. Chain of infection

The traditional epidemiologic triad elucidate the dynamic of disease occurrence when an agent leaves its reservoir (natural habitat|) to colonise a host under some favourable environmental circumstances (see Figure 3). Benenson A.S. (as cited in Park K., 2009) defined a source of infection or reservoir as ‘any person, animal, object, soil, plant or substance (or combination of these) in which an infectious agent lives and multiplies, on which its depends primarily for survival, and where it reproduces itself in such manner that it can be transmitted to a susceptible host”.[18]

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Figure 3:Epidemiologic triad Host Agent Environnement

The HIV is found in a human reservoir where its replicates and cause AIDS. The virus is a RNA virus transmitted mostly sexually and vertically from the mother to the child. The chain of infection in unborn babies and neonates passes through some “portal of exit” (placenta, vaginal secretions or fluid, breast milk) to some ‘’portal of entry’’ in the newborn (Immune cells, skin lacerations, gastro-intestinal tract).

1.3. Mode of transmission

After an agent exits its natural habitat, it can be transmitted to a susceptible host in many ways:

-Directly: by contact or droplet spread
-Indirectly: airborne (e.g. Tuberculosis), vector borne (e.g. malaria).

The transmission of HIV to the neonates is a vertical direct transmission of the virus from the mother to her child during pregnancy (ante partum), during labour and delivery (intrapartum) or breastfeeding (postpartum). [9] Without interventions almost 40 % of HIV-exposed infants will contract the virus and mostly 50 %of them will die before their first birthday (see figure4). The transmission occurs when the two blood circulation systems are in contact, meaning measures should be put in place during labour and delivery, time of high risk, to avoid the two circulation contact. These include reducing contact with blood serum and liquid for the labour attendant as well as avoiding any kind of intervention like episiotomy unless highly recommended.(Akani C akani,2006) [1]. The diagnosis of HIV in early stage of life is a key determinant for the reduction of vertical transmission of HIV at different levels.

Figure 4: Percentage of HIV transmission in exposed infants

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2. Evidence-based of PMTCT interventions

2.1. Material and methodology

For this research paper focused on PMTCT, we selected data for 3 years study from 2008 to 2010.This was a retrospective cohort study. The data included all pregnant women who attended ANC, those who were counselled and tested for HIV and those who delivered at the facility. Our indicators for the PMTCT interventions were pregnant women on HIV treatment (short course or full HAART), the number of HIV exposed babies who tested positive by DNAPCR and HIV antibody testing, the still births and those initiated on HIV prophylaxis. Patients’ registers from Maternity, ANC, paediatric ward, laboratory, and ART clinic and hospital annual report were used.

2.2. Diagnostic of HIV in neonates and infants.

The gold standard of the diagnosis of HIV infection in neonates is based on the finding of the virus genomic material in the neonates’ blood. The test is called ’’DNA PCR”.

In 1989, scientists selected a polymerase chain reaction (PCR) as the major scientific innovation of the year. [7] This is the only acceptable test recommended actually for the diagnosis of HIV in children below 18 months of age though its limitations in some cases with high rate of false positive(Shah I,2004) .[19] The RNA PCR test is used only for monitoring of the virus in infected patients especially when they are on treatment. In some settings, RNA PCR is used as a confirmatory test because it has been shown somewhat more sensitive. The HIV viral culture is more accurate but very expensive for screening in routine practice. The antibody tests are not reliable for babies because they cannot distinguish between maternal and infant HIV antibodies. In medicine, the accuracy of a test is measured by its sensitivity and specificity.

In our setting, two DNA PCR test are recommended to confirm the diagnosis of HIV in exposed infants. One is done at 6 weeks or soon as after and another one at 6 months. A rapid test (HIV antibody test) is also done for all infected children at 18 months. If a child is breastfeeding, he is still at risk of HIV throughout the time of breastfeeding. A confirmatory test is performed 1 week after cessation of breastfeeding if tested negative previously.

Details

Seiten
23
Jahr
2011
ISBN (Buch)
9783640909414
Dateigröße
645 KB
Sprache
Englisch
Katalognummer
v171530
Institution / Hochschule
Atlantic International University – School of Human and social studies
Note
A
Schlagworte
clinical epidemiological analysis hiv-exposed infants resource setting evidence-based pmtct interventions

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Titel: Clinical and Epidemiological Analysis for HIV-exposed Infants in a Low Resource Setting: Evidence-based of PMTCT Interventions