Review
Perinatal tuberculosis and HIV-1: considerations for resource-limited settings

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Clinical features in mothers

Pregnancy can mask the clinical manifestations of tuberculosis; women may be symptom-free,37 have limited symptoms including cough, fever, and fatigue, or severe symptoms such as haemoptysis and weight loss.29, 38, 40 As in the non-pregnant adult,41 pulmonary tuberculosis is by far the commonest detected form of the disease; changes include bronchopneumonia, cavitation, bronchiectasis, and interstitial pneumonitis. Extrapulmonary tuberculosis occurs in 5–10% of pregnant women who are not

Maternal mortality

With HIV-1 coinfection, increasing maternal deaths associated with tuberculosis have been reported from endemic areas. In Lusaka, Zambia, tuberculosis-associated deaths in pregnancy increased from 0% in the 1970s to 14% (36/251) by 1997. 92% of this escalation was HIV-1 associated.13 More importantly, increased maternal mortality due to tuberculosis has been documented in some of the 22 highest-burdened countries responsible for 80% of the global tuberculosis incidence.46 In a South African

Perinatal transmission of Mycobacterium tuberculosis

Little is known about the epidemiology of perinatal exposure of the fetus and newborn to tubercle bacilli, since both are difficult to establish quantitatively.49 Assuming that the mother is the source of infection for congenitally or perinatally acquired tuberculosis in the newborn, the materno-fetal model provides a tight window for quantifying the dynamics of exposure, infection, and disease. The greatest limitation to this quantification is the lack of a gold standard for diagnosis of

Tuberculosis/HIV-1 disease progression due to pregnancy

Women between the ages of 15 and 49 years carry the greatest risk of converting from tuberculosis infection to disease.54 In the pre-chemotherapeutic era, pregnancy was believed to aggravate tuberculosis but evidence has since shown that pregnancy has few adverse effects on the course of tuberculosis.29, 38, 40 This debate on the effects of pregnancy on tuberculosis resurfaces within the context of the HIV-1 epidemic, considering its dramatic effects on the immune system. The CD4 lymphocyte is

Investigating the HIV-1-infected mother with suspected tuberculosis

The high-risk mother may be identified by her history of contact with recent tuberculosis (family or other), and/or suspicious clinical signs or symptoms. Other high-risk groups include the malnourished, homeless, socio-economically impoverished mother, the alcoholic/drug-abusing mother, or mother with immunosuppressive illnesses such as diabetes mellitus. Since tuberculosis is the commonest chronic infection in Africans with HIV-1, all mothers who are HIV-1 positive should be carefully

Management of tuberculosis in HIV-1-infected pregnant women

The attending physician may be faced with three different clinical scenarios in HIV-1-infected women with tuberculosis during pregnancy. Firstly, the mother may be symptomatic. Secondly, symptoms and signs may emerge only during the peripartum or postpartum periods. And thirdly, the mother may be symptom-free or mildly symptomatic with the detection of tuberculosis in their infants the first and only clue to maternal disease.

Once tuberculosis is diagnosed or highly suspected, treatment with

To improve maternal health

One-third of the HIV-1-infected adults with tuberculosis have a CD4 concentration of fewer than 200 cells/μL.28, 68 For HIV-1-infected pregnant women without tuberculosis this figure is 13·6–18·6%.69 Local guidelines for therapy in developing countries are often based on CD4 suppression below 200 cells/μL or clinical stage IV disease;70 as a result not all mothers will necessarily qualify for antiretroviral therapy.

To reduce vertical transmission of HIV-1

Apart from the direct issues of antiretroviral therapy affecting maternal

Effect of combined antiretroviral and antituberculosis therapy

Most tuberculosis regimens have minimum maternal and fetal effects74 but complexities in combination with antiretrovirals are multiple. Pharmacokinetic, physiological, and disease-mediated mechanisms may affect the absorption, distribution, uptake, and elimination of the drugs used (panel 1). Drugs that are considered safe in pregnancy (table 2, table 3) should be used, administered under the guidance of an experienced clinical team, and tailored to suit the individual patient.

Apart from the

Breastfeeding advice in resource-limited environments

WHO/UNAIDS/UNICEF recommends86 that breastfeeding is supported by proper voluntary counselling and testing, to enable mothers to make accurate choices about feeding. Alternatives to breast feeding may be adopted in situations where they are feasible, safe, affordable, and sustainable.

In general, the decision to breastfeed should not be affected by tuberculosis in the mother, with the exception of tuberculosis breast abscess, in which case breastfeeding is discontinued from the affected breast.

The HIV-1-infected mother with MDR-TB

MDR-TB is uncommon in sub-Saharan Africa, and its spread does not generally seem to be aggravated by HIV-1;87 nor does it appear to be more aggressively transmitted from mother to newborn.28 A diagnosis of MDR-TB can only be made based on susceptibility testing of cultured samples, and is never made on suspicion. The diagnosis of MDR-TB should be considered in a mother with culture/microscopy-confirmed tuberculosis, who is compliant with antituberculosis therapy, but remains clinically ill and

Perinatal tuberculosis in babies

Tuberculosis detected in the newborn may be acquired (a) in utero, through haematogenous dissemination via umbilical vein, aspiration of infected amniotic fluid, or ingestion of infected amniotic fluid; (b) intrapartum, through aspiration or ingestion of tuberculous amniotic fluid or cervicovaginal secretions at birth; or (c) postpartum, through breastfeeding (ingestion of infected milk), inhalation, or ingestion of infected respiratory droplets from an infectious source, usually the mother.88

Clinical features of perinatal tuberculosis

The common clinical features of newborn babies with tuberculosis are described in panel 2. Few cases21, 22, 91, 92 of congenital tuberculosis in association with HIV-1 coinfection have been described. Clinical signs may be similar to earlier descriptions in the pre HIV-1 era. Where both infections are acquired, the course may be one of rapidly progressive HIV-1 disease.91 With highly active antiretroviral therapy (HAART) this deterioration may be slowed. Diseases due to immunodeficiency,

Diagnosis of perinatal tuberculosis

Babies at risk for perinatal tuberculosis include those whose mothers have proven or suspected tuberculosis disease during pregnancy. Failure to investigate appropriately may result in a missed diagnosis and contribute to mortality, especially as signs of disease may not appear until several days or weeks later if the infection is transmitted peripartum rather than intrauterine.

Confirmation of diagnosis is based on the detection of acid-fast bacilli on smear microscopy, and/or culture of M

Investigations

Since tuberculosis develops slowly and it is possible for the recently infected baby to appear well early on, both the apparently well baby and the symptomatic baby should be investigated for vertical transfer of M tuberculosis (figure 1). Early-morning prefeed buffered gastric washings and/or nasopharyngeal aspirate,93 submitted for smear microscopic detection of acid-fast bacilli and M tuberculosis culture,21 should be undertaken, together with a chest radiograph (figure 2). In the

Preventing perinatal tuberculosis in HIV-1-infected pregnant women in the developing world: what could the future hold?

In addition to a high index of suspicion, timely investigations and appropriate treatment of the tuberculosis-diseased pregnant woman and her close contacts, including her baby, are required. This demands awareness by all health-care workers, that a newborn infant forms a dyad with its mother, and that investigation and management of recent parturients who are ill must include the newborn

In addition to optimising established tuberculosis-control strategies,100, 101 one component in reducing the

Search strategy and selection criteria

Data for this review were identified through PubMed and Medline searches using several combinations of the search terms “tuberculosis”, “congenital”, “perinatal”, “infant”, “HIV-1”, and “maternal mortality”, and references from relevant articles retrieved. Only human studies were selected. Websites from organisations including the WHO, National Institutes of Health USA, US Centers for Disease Control and Prevention, and Johns Hopkins University AIDS education site were searched for relevant

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