transmission (MTCT) of HIV infection can occur in utero, during labour and delivery or through breastmilk, with the bulk of transmission occurring in the intra-partum period44. Transmission rates vary from less than 2% in the developed world due to the use of highly active antiretroviral therapy (HAART), elective caesarean section and safe replacement feeding, to more than 30% in the developing world without access to antiretroviral prophylaxis and with prolonged breast-feeding45. MTCT rates vary in South Africa from 2% to 30% depending on use of interventions to prevent MTCT and the duration and method of breast-feeding46.Factors that are associated with MTCT transmission are as follows:
Maternal risk factors
These include advanced maternal disease or surrogate markers thereof, including viral load and CD4+ count, viral phenotype and genotype, smoking or other substance abuse, lack of ARV therapy or ARV resistance, sexually transmitted infections (STIs) or other co-infections and sexual behaviour.
Obstetric risk factors
These include vaginal or pre-term delivery, prolonged rupture of membranes, placental disruption or abruption, chorio-amnionitis, invasive fetal monitoring, and episiotomy or use of forceps.
Neonatal risk factors
Major factors include prematurity, oral thrush, gender and exposure to infected breastmilk.
world’s population. Over 8 million new TB cases occur annually and 60% of cases occur in only 10 countries (see Table VII). In addition close to 2 million TB-related deaths occur annually; it is responsible for more deaths than any other curable infectious disease. TB is a leading killer of young adults in their most productive years. The WHO estimates that infected adults lose an average 3–4 months of work while recuperating from the disease, while society loses an average of 15 years of economic activity from each adult TB death. The WHO has declared TB to be a global emergency and has called for urgent and extraordinary action49.
The global burden of TB is increasing, largely due to the spread of HIV/AIDS. HIV- infected subjects are far more susceptible to TB, are more difficult to diagnose, and in addition, are also more difficult to treat. TB lifetime risk in HIV-uninfected residents of southern Africa is approximately 10%; in HIV-infected people, this approaches 10% per annum. Furthermore, HIV-infected people have a much higher mortality in the period following TB treatment, with 30% dying within a year of diagnosis and treatment. In addition, smear-negative TB is far more common in HIV-infected individuals (estimated to be as high as 50%), requiring sophisticated imaging and laboratory techniques to make the diagnosis50.
With the HIV epidemic continuing to spread at alarming rates both nationally and globally, it is anticipated that this will contribute to the increasing numbers of TB cases.
Source: World Health Organization, September 2003
All cases (per 100 0000)
≥ 300 100 < 300 50 < 100 10 < 50
< 10
The presentation of material on the maps contained herein does not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or areas or of its authorities, or concerning the delineation of its frontiers or boundaries.
Date Source: WHO Stop TP Map Production:
Public Health Mapping Group Communicable Diseases (CDS) World Health Organization
Figure 3. Estimated tuberculosis incidence – 200349
In addition, the diagnosis of TB continues to be problematic, particularly in infants and young children. Diagnostic assays for TB have not developed at the pace of diagnostic tests for other disease, and significant investment is urgently needed to improve their sophistication.
The escalation of the TB epidemic worldwide has occurred despite the availability and widespread use of Bacillus Calmette-Guérin (BCG) vaccine and the use of directly observed therapy short course (DOTS) for persons diagnosed with active disease. BCG is currently the only licensed vaccine. BCG affords ~80% protection against tuberculous meningitis and miliary tuberculosis in infants and in young children, but protection against lung disease, at all ages, and has been variable. DOTS, the global control strategy aimed at controlling TB transmission through prompt diagnosis of symptomatic smear- positive disease, has failed to prevent rising tuberculosis incidence rates in many parts of the world49.
Annually, over 250 000 new cases of tuberculosis (TB) occur in South Africa. The estimated annual incidence rate of TB is in excess of 700/100 000 population and in some areas the rate exceeds 1 000/100 000 (1%). In SA, rates vary between provinces with the Western Cape, which accounts for only 10% of the SA population, bearing the brunt of the epidemic, with 25% of the case load (Figure 4). Children account for 15–20% of the TB case load. The high burden of childhood TB reflects recent transmission within the Table VII. Top 10 high TB burden countries49
Country
Population All TB cases TB cases per
1000’s 1000’s 100 000 pop
1. India 1 087 124 1 824 168
2. China 1 307 989 1 325 101
3. Indonesia 220 077 539 245
4. Nigeria 128 709 374 290
5. South Africa 47 208 339 718
6. Bangladesh 139 215 319 229
7. Pakistan 154 794 281 181
8. Ethiopia 75 600 267 353
9. Phillipines 81 617 239 293
10. Kenya 33 467 207 619
Source: WHO report 2006: Global Tuberculosis Control
population and is representative of the failure of TB control measures. Children contribute little to the maintenance of the TB epidemic, but they suffer severe consequences such as miliary or disseminated disease and meningitis. TB is currently one of the leading causes of death in adults and children in South Africa and the case fatality rate has increased from 3% in 1993 to 7.4% in 2003. A major reason for the escalation of the TB epidemic in South Africa is the evolution of the AIDS epidemic. It is estimated that approximately 60% of adult TB cases aged 15–49 years are HIV co-infected51.
In the 1970s, after confirmation that short-course (6 months) TB therapy was highly effective, the prospect of TB eradication led to renewed vigour in tackling TB as a public health issue. Despite the availability of effective therapy, and the implementation of improved directly observed therapy short course (DOTS) programmes in the mid-1990s, southern Africa continues to have a TB problem that is growing, fuelled by a growing HIV epidemic. The WHO advocates treatment of infectious (smear-positive) TB as the
≥ 900/100 000 population 700–899/100 000 population 500–699/100 000 population 300–499/100 000 population
≤ 299/100 000 population
Limpopo
Mpumalanga Gauteng
North West
Free State
Eastern Cape
Kwazulu-Natal Northern Cape
Western Cape
Figure 4. TB incidence in 2004
most cost-effective method in tackling TB control. The DOTS programme emphasises five key components, including:
political commitment
■
access to improved sputum microscopy
■
access to standardised treatment using quality assured drugs in a monitored
■
environment
uninterrupted drug supply, and
■
improved programme monitoring.
■
Even in countries with a large commitment to DOTS, such as Botswana, the impact of DOTS on TB numbers has been disappointing. In Peru and China, DOTS appears to have had significant impact, but neither country has a generalised HIV epidemic as is present in southern Africa. The DOTS approach itself is contested, with three trials assessing the effect of the approach showing conflicting results (two showing no effect52, 53, including one done in SA, the third in Thailand54 showing significant effect).
In developed countries, a modified DOTS approach that includes aggressive patient support and follow-up of defaulters has yielded impressive results, especially in the United States54.
Effective treatment of TB is available, but cure rates remain unacceptably low in South Africa, despite clear guidelines and standardised drug formulations, including fixed dose formulations. Not a single South African province has attained the 85% cure target set by the WHO55. Diagnosis remains challenging, with many areas still relying on unreliable and laborious microscopy techniques developed in the 19th century. The time from onset of symptoms to initiation of treatment in African countries is estimated to be 3–4 months in patients with smear-positive TB. Finally, treatment of TB is estimated by the WHO to be over $700/patient in SA, significantly more than in other high-TB burden countries, largely owing to the high cost of labour, the cost determines who can provide drug treatment55. The indirect economic consequences described above are likely to be far in excess of this figure.
In resource-poor areas, a reliance on the clinical diagnosis of TB leads to confused and inconsistent treatment protocols, and may contribute to the development of multidrug-resistant (MDR) TB. The rate of MDR TB, a further problem, made famous by the 1991 outbreak in New York is estimated to be at 1.7% in South Africa (6.6%
of retreatment cases), with over 6000 cases annually. Due to South Africa’s large TB caseload, this translates into the highest absolute number of MDR TB cases in the world. MDR TB is defined as resistance to at least two of the most effective anti-TB drugs, rifampicin and isoniazid. MDR TB identification requires relatively sophisticated and expensive laboratory facilities. MDR TB treatment is complex, prolonged and very expensive, with a significant failure rate, resulting in further TB mortality. In the case
of HIV, MDR TB appears to be particularly aggressive, and usually progresses rapidly to death, in the absence of antiretrovirals56–59.
A recent outbreak of extensively drug-resistant (XDR), (generally known inappropriately as extremely drug resistant) TB has been described in several provinces within South Africa, mainly amongst HIV-infected patients59. In addition to resistance to rifampicin and isoniazid, XDR TB is defined as resistance to at least three of the six classes of the drugs available to treat MDR TB. The outbreak was associated with a very high mortality, despite the availability of antiretrovirals in many cases: 52/53 patients in the original report died, with an average time to death of 16 days from sputum collection. While XDR cases have been described previously in South Africa, the sheer number of cases and the high mortality, including deaths of health care workers, attracted significant attention. In the cohort studied, 39% of patients had MDR TB, it associated with significant mortality in both HIV-uninfected and in particular HIV- infected individuals56, 60.
A report on progress of the epidemic revealed successful completion of treatment in only 65% of patients, cure in only half, and a defaulter rate of 11.5 % in 2003. Interestingly, KwaZulu-Natal (completion rate of 55% and cure rate of 35%) and Mpumalanga (50%
and 32%), the sites where MDR and XDR have been identified as severe problems, fared worst; both provinces have very high prevalence of drug resistance. Treatment of MDR TB in terms of drug costs alone is estimated at R28 000 per patient56, 60.
Both MDR and XDR TB have at their root poor management of the systems providing treatment to people with TB. In particular, in South Africa poor prescribing practices, interrupted drug supply and poor support to patients attending the clinics, along with poor infection control measures, have fuelled the resistant TB epidemic. The TB programme has often been divorced from the HIV control programme, although it is clear that HIV is a major driver of the epidemic. International efforts to achieve patient- centred case management have had limited success, despite claiming improved coverage of the country with the DOTS approach. The XDR outbreak has brought renewed calls for expansion of laboratory techniques for diagnosis of resistant TB to be made more widely available. A recent editorial in the Lancet has by contrast called for a “back-to- basics” approach that emphasizes strengthening of the public health strengthening at a primary care level, rather than a focus on solely improving access to second-line TB drugs and diagnostics60.
Evidence-based practice and recommendations
The objectives of this chapter, a narrative review, are firstly to define the concept of scientific evidence-based policy and practice (evidence-based medicine, nutrition and/or health practice); secondly, to review briefly the different types of nutritional studies that could and should be considered and used in gathering the available evidence or standard of proof, indicating both strengths and weaknesses of such studies; and thirdly, to show how the quality of evidence from different types of sources can be evaluated, judged and graded to determine the strength of recommendations for formulation of policy and practice.