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The Clinical Patterns

HIV infection causes essentially the same immunosuppression in all of its hosts, but the clinical presentation and complications of AIDS in the tropics differ because of preexisting conditions in the host and the host's environment, many of which also contribute to immunosuppression. These include poor hygiene, poor living conditions, preexisting infections (especially parasites), chronic debilitating diseases, nutritional deficiencies, reduced accessibility to diagnosis and treatment and, possibly but unlikely, unknown factors such as genetic predisposition. This variable background also affects the patterns of spread and the progression from infection to AIDS, as well as the time from the development of AIDS to death.

When AIDS does develop, almost any system may be involved. There may be myocarditis, pericarditis, and endocarditis, and opportunistic infections presenting as oral thrush, esophagitis, gastritis, and colitis. Lymphadenopathy, particularly abdominal, may be nonspecific or tuberculous or from atypical mycobacteriosis. There may be cystitis, pyelonephritis, renal abscesses, nephropathy, and renal insufficiency. HIV-neuropathy causes various neurological symptoms, such as microcephaly, delayed development, ataxia, seizures, dementia and coma.

In much of the tropics, tuberculosis and the gastrointestinal manifestations of AIDS predominate. M. tuberculosis is the most common significant pathogen and gastrointestinal disease the most common clinical presentation. Common Western pathogens, such as P. carinii and atypical mycobacteria are rare in many regions, but both groups, tropical and temperate, share other complications such as Kaposi's sarcoma, although not always in the same way. Children with AIDS have their own diagnostic problems. Many of the clinical signs and symptoms resemble common childhood complaints (disscussed later).

Clinical Definitions of AIDS

Clinical criteria to define AIDS have been developed by the World Health Organization for use in sub-Saharan Africa and elsewhere to allow the diagnosis of AIDS without laboratory testing. Clinical definitions vary considerably in different locations depending on the local prevalence of opportunistic diseases and the sophistication of diagnostic procedures available. The sensitivity of the clinical definition developed for sub-Saharan Africa has ranged from about 33% to 65%, with a specificity of 78%-90%.

Relying on clinical criteria alone has certain drawbacks. For example, in Africa, the present system includes persistent cough as one of the minor criteria, and severe weight loss and persistent fever as major criteria, making it difficult to distinguish patients with tuberculosis from those with AIDS. Even in patients known to be HIV positive, the presence of pulmonary tuberculosis and the accompanying symptoms need not indicate progression to AIDS. As another example, a common manifestation of AIDS in Africa is "slim disease," manifested by weight loss, chronic diarrhea, and chronic fever. This was incorporated into one definition of the HIV-related wasting syndrome, but only if not associated with other conditions such as cryptosporidiosis or tuberculosis which might cause similar findings. However, in many cases, these other diseases are related to HIV and it is often difficult in Africa to exclude such concurrent diseases. It has been suggested that in Africa, the HIV-related wasting syndrome might better be defined as requiring greater than 10% weight loss, chronic diarrhea for at least 30 days, and chronic fever for at least 30 days, whether or not there are concomitant diseases which might be responsible for these findings.

A population study in Tanzania by Todd and colleagues showed that the proportion of adult deaths attributable to HIV was 35% overall and 53% in the 20-29 age group. However, the applicable WHO clinical case definition of AIDS was satisfied for only 18% of deaths occurring in HlV-positive patients because many signs and symptoms associated with HIV deaths were nonspecific.

A clinical definition of AIDS has been developed for South America, applicable to developing countries with adequate serological facilities but without other sophisticated diagnostic procedures. Clinical criteria in South America differ from those used in Africa: diarrhea and weight loss are less common in South American patients, so cachexia was substituted. The South American definition also has the advantage of including symptoms of central nervous system dysfunction. Using a complex scoring system of symptomatolology and documented diseases, this system achieves relatively high specificity and sensitivity.

Clinical definitions of AIDS should ideally be equated with a laboratory standard such as a CD4 count of less than 200 cells per mm³. However, it is unlikely that even tailored clinical definitions can be accurate in locations where there are high endemic rates of diseases which are also HIV associated, such as tuberculosis and Kaposi's sarcoma.

Infants, Children, and AIDS

Thirty percent or more of children born to HIV-seropositive mothers will themselves become seropositive, and their AIDS incubation period will be shorter, with clinical signs and symptoms appearing relatively quickly. However, HIV-1 serological tests in infants must be interpreted with caution because maternal antibodies may persist for as long as 15 months. Thus, if there are no clinical indications of disease, a positive serological test in an infant under 15 months may not indicate infection and may revert to negative. If the child is antibody positive after age 15 months, he or she is probably infected. When available, viral culture, in vitro production of antibodies, or polymerase chain reaction testing can resolve this dilemma.

Children with AIDS have their own special diagnostic problems. Many of the clinical signs and symptoms of the disease are similar to other common childhood complaints, such as measles (often a severe disease in the tropics), malaria, failure to thrive, chronic cough and fevers, recurrent diarrhea, and respiratory disease. The difficulties are exemplified by pneumonia, which in the developing world is the cause of death of 30% of children under the age of 5 years, even without AIDS. Distinguishing between bacterial pneumonia and tuberculosis and determining which patient might harbor HIV is a major diagnostic challenge, especially where laboratory and imaging facilities are limited or nonexistent. In some regions, Burkitt's lyinphoma and acute Kaposi's sarcoma of childhood are endemic and their presence is not AIDS defining.

In the study by Vetter et al of children hospitalized in Abidjan, Ivory Coast, the most common reasons for hospital admission in HIV-positive children were respiratory infection and malnutrition. Mortality was 2.4 times higher in HIV-positive children compared with HIV-negative hospitalized children. Most pneumonias in pediatric AIDS are caused by common bacterial pathogens, but if there are severe respiratory signs with any interstitial pneumonia, and a poor response to antibiotics, P. carinii pneumonia should be considered, even though it is rare in some countries. On the other hand, lymphocytic interstitial pneumonitis, a persistent interstitial micronodular pulmonary parenchymal pattern, may have minimal respiratory signs.

In an autopsy study of children with AIDS, also from Abidjan, respiratory infections, P. carinii pneumonia, and measles were common as compared with HIV-negative deaths, while pyogenic meningitis was common in both groups. Surprisingly, in HIV-positive children, tuberculosis, lymphocytic interstitial pneumonitis, and HIV encephalitis were rarely found at autopsy. In a study from Zambia, high HIV rates were found in children with tuberculosis (69%), malnutrition (41%), pneumonia (28%), and diarrhea (24%). HIV may be responsible for various neurological symptoms in children, including rnicrocephaly, delayed development, ataxia, seizures, and coma.

Malaria and Transfusion-Related AIDS

Malaria, particularly infection with Plasmodium falciparum, is an immense public health problem in Africa and many other tropical countries, made worse by the increase in drug-resistant strains. Fortunately, concomitant HIV infection does not seem to increase the chances of clinically significant malarial episodes, or change the rate of progression from HIV to AIDS. Indeed, there has even been some evidence that malaria or the chloroquine used to treat malaria may have some effect against HIV. An elegant longitudinal study from Mama Yemo Hospital in Kinshasa, Zaire, showed no difference in malarial rates in a group of children who had been exposed to HIV in utero, some of whom were HIV positive, some of whom had advanced AIDS, and some of whom were HIV negative or had reverted to the HIV-negative state after birth. These findings are confirmed by numerous other studies.

However, the severe anemia caused by malaria may necessitate transfusion, which presents a substantial risk for AIDS and other blood-borne diseases. For example, 87% of transfusions in Kinshasa are performed for malaria and 6% of the blood donors are HIV-positiveChikwem et al's study of donated blood in Nigeria revealed that among 364 healthy donors, 14.9% showed hepatitis B, 5.8% HIV-1, 4.1% Plasmodium falciparum, and 3.6% Treponema pallidum. Worldwide, HIV-positive blood is transfused either because the blood is not properly tested or because blood must be given in an emergency,whether or not it has been tested, and testing may be a lengthy process. Needles may be reused without effective sterilization. The risk of transfusion-related AIDS is found over much of the malarial world, compounded in some regions (such as West Africa), by the high prevalence of hemoglobinopathies which also require transfusion.

Falciparum malaria is the most common cause of anemia of pregnancy in sub-Saharan Africa. Malarial parasitemia is highest in the 13th-16th weeks of pregnancy and, for unknown reasons, the rise is most significant in the primagravida patients. It is not, however, the only cause of anemia: parasites, malnutrition, high fertility rates, and chronic ill health all contribute. In Zaire, examination of 2,950 untreated pregnancies revealed that 72% of patients had a moderate anemia (hemoglobin level 7-11) and 3.7% of patients had severe anemia (hemoglobin under 7). A 50% mortality is observed when the hematocrit is less than 13% and there is concomitant heart failure. Because the anemia of pregnancy is often treated by transfusion with inadequately screened blood, it is an important cause of AIDS in the maternal and fetal populations.

Leprosy and AIDS

Although far less common than Mycobacterium tuberculosis, Mycobacterium leprae is still a significant public health problem in sub-Saharan Africa, India, and other developing countries in Asia, the Middle East, the Caribbean, and Haiti (see Chapter 34 on Leprosy). There has been concern that, due to immunosuppression, HIV may increase susceptibility to leprosy. Data are mixed on this subject. A study in Zambia demonstrated a markedly increased incidence of HIV infection in new leprosy patients as compared with controls, whereas a larger study of leprosy patients in the Ivory Coast, Senegal, and Yemen noted equal HIV-positivity rates. In a primate model of leprosy, inoculation led to increased leprosy infection rates in those animals which were SIV positive. It has also been postulated (but not proven) that HIV infection may accelerate the development of clinical leprosy, and that active chronic infection with leprosy may accelerate the course of HIV disease due to the preexisting immune response. In Haiti, although HIV-positive rates in leprosy patients were the same as in the general population, the HIV-positive leprosy patients progressed to symptomatic AIDS more rapidly than would be expected. It also appears that leprosy relapses are more common in HIV-infected individuals.

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Copyright: Palmer and Reeder