Reactions of Ugandan antisera with peptides encoded by V3 loop epitopes of human immunodeficiency virus type 1.

The specificities of antibodies reacting with peptides encoded by V3 loop apical epitopes were determined for sera from 230 seropositive Ugandans, including asymptomatic persons and AIDS patients, sampled between 1986 and 1992. Most (71%) of the sera reacted with the peptide encoded by HIV-MN, 59% reacted with a peptide containing a consensus sequence for Ugandan variants of the HIV-1 global subtype A (referred to as the Uganda A consensus), 59% reacted with a peptide containing a consensus sequence for Ugandan variants of the global subtype D (the Uganda D consensus); 19% of the sera also reacted with peptides encoded by the divergent Ugandan variant U31. There was no obvious correlation between the specificities of antibody binding and the V3 loop sequence of the corresponding virus isolate or provirus. Competitive inhibition and antibody adsorption experiments indicated that the MN peptide, the Uganda A consensus peptide, the Uganda D consensus peptide, and the U31 peptide were recognized by different sets of antibodies. Eighteen percent of the sera from AIDS patients and 26% of the sera from asymptomatic persons were monospecific for one of the MN, Uganda A, or Uganda D peptides. Whereas all except one of the singly reactive AIDS sera were specific for MN, 39% of the singly reactive asymptomatic sera were specific for MN, 39% for the Uganda A peptide, and 21% for the Uganda D peptides. We conclude that analysis of the specificities of antibodies against the V3 loop epitopes in sera from asymptomatic persons could provide useful epidemiological data about the prevalence of viral subtypes within a population.

PIP: The specificities of antibodies reacting with peptides encoded by V3 loop apical epitopes were determined for sera from 230 HIV seropositive Ugandans, including 123 asymptomatic persons and 107 AIDS patients, mostly mothers attending prenatal clinics, sampled between 1986 and 1992. 71% of the sera reacted with the peptide encoded by HIV-MN, 59% reacted with a peptide containing a consensus sequence for Ugandan variants of the HIV-1 global subtype A (referred to as the Uganda A consensus); 59% reacted with a peptide containing a consensus sequence for Ugandan variants of the global subtype D (the Uganda D consensus); and 19% of the sera also reacted with peptides encoded by the divergent Ugandan variant U31. Although 70% of the 1986 sera reacted with the Uganda A consensus peptide, only 49% of the 1991/92 sera reacted with this peptide (p 0.005). 20% of the 1991/92 sera, compared with only 7% of the 1986 sera, did not react with any of the peptides (p 0.05). There was no obvious correlation between the specificities of antibody binding and the V3 loop sequence of the corresponding virus isolate or provirus. Competitive inhibition and antibody adsorption experiments indicated that the MN peptide, the Uganda A consensus peptide, the Uganda D consensus peptide, and the U31 peptide were recognized by different sets of antibodies. 18% of the sera from AIDS patients and 26% of the sera from asymptomatic persons were monospecific for one of the MN, Uganda A, or Uganda D peptides. Whereas all except one of the singly reactive AIDS sera were specific for MN, 39% of the singly reactive asymptomatic sera were specific for MN, 39% for the Uganda A peptide, and 21% for the Uganda D peptides. The analysis of the specificities of antibodies against the V3 loop epitopes in sera from asymptomatic persons could provide useful epidemiological data about the prevalence of viral subtypes within a population.

A review and assessment of non-governmental organization-based STD/AIDS education and prevention projects for marginalized groups.

A review of projects run by non-governmental organizations (NGOs) in primarily developing countries, which have aimed to provide STD/AIDS education and prevention skills to various marginalized groups, reveals that past quantitative and formative research has failed to identify key programmatic factors which lead to more successful project implementation and sustainability. In observations, interviews with field staff, visits to program sites and information drawn from the literature, a variety of methods to reach a wide range of groups such as men who have sex with men, prostitutes, clients of prostitutes, prisoners, street children, migrant workers and refugees are explored. Factors found to facilitate project success include the following: at least one full-time committed staff member; respectful treatment and appropriate motivation of the target group; suitable and sufficient equipment and supplies (particularly condoms); planning ahead for the participation of HIV-positive individuals and ways to meet their needs; focusing on qualitative rather than quantitative evaluation; planning in advance beyond a 9 or 12 month 'model'. Despite some evidence that marginalized groups can be successfully motivated to practise safer sex through prevention education, long-term behaviour change still presents major challenges--even when specific conditions are met.

Nucleotide sequence of a Ugandan HIV-1 provirus reveals genetic diversity from other HIV-1 isolates.

A Ugandan isolate of human immunodeficiency virus type 1 (HIV-1), designated U455, was adapted to growth in U937 cells, the provirus cloned into the lambda L47.1 vector, and its DNA sequence determined. The sequences of some of the U455 genes showed a marked divergence from those of North American and other African isolates. The sequenced clone was defective with single in-phase stop codons in the vpr and env genes and frame shift, resulting in a stop codon, within the vpu gene.

HIV: implications for blood transfusion and banking in Africa.

PIP: African countries with an appreciable HIV problem receive assistance in screening blood for HIV antibodies as part of WHO's Global Program on AIDS (GPA). This article describes the health problems with blood transfusions and offers suggestions on ways to minimize the prevalence of HIV in blood banks. Ways to minimize blood transfusions include appropriate use of plasma volume expanders and electrolyte solutions. Stopping the practice of using soldiers and prisoners as group blood donors and substituting secondary school students as donors was recommended to prevent HIV contamination of the blood banks. Since HIV antibody tests are being improved and simplified, HIV test kits should not be ordered too far in advance. To verify a positive test, the use of 2 differently manufactured ELISA tests on each positive blood sample was recommended because most African labs do not have the expertise or money to do Western blot analysis. Testing facilities were advised to tell blood donors with donated HIV positive blood that they were infected and hopefully this would help minimize the possibility that the infected individual would infect others.^ieng

Prevalence of HIV-1 in east African lorry drivers.

Sixty-eight lorry drivers and their assistants were examined for evidence of infection with HIV-1 because of their association and regular contact with prostitutes. Out of a total of 68 drivers, 24 (35.2%) were serologically found to be HIV-1 positive. Epidemiological evidence demonstrated a wide travel history involving seven different countries served by the port of Mombasa. History of other sexually transmitted disorders were significantly higher in HIV-seropositive individuals. The data presented here further support the hypothesis that a major route of heterosexual transmission of HIV in Africa is dissemination through a group such as lorry drivers and their assistants, whose behaviour puts them at risk of acquiring sexually transmitted diseases.

PIP: Participants in the study were drivers and turnboys who passed through a transport depot in Kampala, Uganda, in November 1986. Each participant answered a questionnaire aimed at determining basic demographic data, countries visited within the previous 3 years, level of prostitute contact within those countries, and whether they had had a history of urethral discharge or genital ulceration. A total of 45 drivers and 23 turnboys with a mean age of 38 and 26 years, respectively, were interviewed and blood samples were taken. Serological controls were selected from people of the same age as the study group from individuals donating blood. Serum immunoglobulin (Ig) antibodies to HIV were determined by a competitive enzyme-linked immunosorbent assay and a competitive ELISA using recombinant HIV core and envelope proteins. All serological results were verified by immunoblot assays or were prepared by electrophoretic separation of U937 cell lysates infected with a Ugandan HIV-1 isolate. Antibodies to Treponema pallidum were detected by a hemagglutination test. They were of Ugandan (66.2%) or Kenyan (33.8% ) origin. All were sexually active, and all denied homosexuality and intravenous drug use. The overall HIV-1 seropositivity rate was 35.2%, compared with the control group of 9.2% (24 out of 68 versus 12 out of 130; p 0.01). Using the antigen detection systems, 7 of the seronegative sera proved to be antigen positive. In addition, 4 out of the 24 seropositive sera (16.6%) also proved to be antigen positive. 36.7% of the population admitted more than 50 lifetime sexual partners. Of the remainder, 83.7% had had more than 10 lifetime sexual partners. The level of urethral discharge and genital ulceration revealed a significant difference (p 0.01) between seropositive and seronegative individuals. The overall level (55.8%) of T. pallidum antibodies among drivers and turnboys was significantly higher than in the control group (p 0.01). The drivers had the highest level of T. pallidum antibodies (62.2%) compared with turnboys (43.8%), reflecting the older average age and, thus, the greater sexual experience.

Precautions against HIV transmission in hospitals.

PIP: This article deals with the precautions necessary for handling blood in a hospital environment. It is known that most people who present to the hospital setting may be unknowingly infected with HIV virus, and thus exposure to blood should be handled with care. Routinely, anyone who is at risk of coming in contact with contaminated blood should wear gloves. The nature of the gloves should differ according to the responsibility at hand. Thus plastic gloves should be used for vaginal examinations, standard rubber gloves for deliveries and surgical operations, and heavy duty gloves for scrubbing floors. Soap and water should be readily available for personnel in the event that presumed infected blood comes in contact with skin. A concentration of 0.5% sodium hypochlorite should always be available in the clinical setting, to treat unforseen blood spills. Instruments contaminated with blood could be adequately handled by using sterilization methods which are commonly in use. Boiling the instrument for 20 minutes in hot water is adequate disinfection. However, this method is not sufficient for fiber optic instruments; instead manufacturer's instruction should be followed. Steam sterilizers or autoclaves are more efficient for surgical instruments such as artery forceps. Clearly, simple methods of disinfection are adequate in killing HIV virus, and given that many people are already infected with HIV, sterilization would be a useful routine to practice in most hospitals in the developing countries.^ieng

Clinical manifestations of AIDS in tropical countries.

PIP: Diagnosis of clinical AIDS can be difficult for clinicians in Africa, where there is only limited access to the sophisticated bacteriological diagnostic facilities needed for diagnoses based on the criteria laid down by the Center for Disease Control in the US. The most common presentation of AIDS in Africa is as an enteropathic condition known as 'Slim.' Based on this and other common presentations of the disease in Africa, a group of clinicians in Bangui, Central African Republic, drew up a list of criteria for the diagnosis of AIDS in Africa which are based on patient history and examination and the exclusion of other conditions rather than on serological confirmation of HIV infection. The major criteria are 1) unexplained fever for longer than 1 month; 2) unexplained diarrhea for longer than 1 month; and 3) weight loss greater than 10% of previous weight. Minor symptoms are presence of a maculopapular rash, oral candidiasis or thrush, herpes zoster or shingles, aggressive or uncontrollable herpes simplex, unexplained cough for longer than 1 month, or enlarged lymph nodes in more than 1 extrainguinal site. The finding of 2 major symptoms and at least 1 minor one is enough for diagnosis. These criteria have been found to be useful. However, they do not cover all the presentations which have been associated with AIDS. Unusual presentations of HIV infected persons which have been seen in Africa include serially developing abscesses in pyomyositis, gall bladder diseases, pericarditis or myocarditis, diseases of the Central Nervous System (cryptococcal meningitis, toxoplasmosis, non-specific leuko-encephalitis, atraumatic paraplegia, acute psychosis or chronic deterioration in mental capacity, lymphoma of the brain), prodromal illnesses, swollen lymph nodes, herpes zoster or shingles in young adults, or tumours of the lymphatic system. Differential diagnosis is extremely important.^ieng

Impact of AIDS in the developing world.

PIP: Some features of the HIV infection are unique to the developing world (as exemplified by Africa, which is the frontline continent for AIDS). The infection affects all social groups, and since it is spread by heterosexual activity, it affects equal numbers of men and women, and the infection of women has dire consequences for population structure. Opportunistic infections are caused by organisms against which there is no effective treatment. Health budgets, with an average of $10 per capita, cannot buy such drugs as are available. Political instability and poverty create a climate favorable to casual sex and prostitution. Infection is highest among adults in their 20s and 30s, when the men are most productive economically, and the women have begun but not completed their childbearing. In Zaire the mean age at infection is 37 for men and 30 for women, and the mean age at death in Zambia is 35 for men and 26 for women. Seroprevalence is as high as 76% (among barmaids in Uganda), and at least half of the spouses of seropositive persons are infected. The number of new cases at 1 hospital in Kampala was 3-8/day in 1986. Using what is known about AIDS and what is know about the population structure in African countries, it is possible to model the impact of AIDS on a typical developing country with a population of 10 million. If seropositivity were 5%, 20.000 cases of AIDS could be expected each year among 15-50-year olds, with an additional 1500 cases among newborns. At least half of the babies of seropositive women will be seropositive. For every adult death, 20 man- or 40 woman-hours of work will be lost. The deaths of young married women will leave an immense burden of sick and dying orphans on extended families whose kinship ties are no longer close enough to cope, in countries which have no institutional facilities for orphan care. The number of opportunistic infections will increase, and, unless AIDS patients are turned away, health resources will be drained from potentially curable diseases. The number of people willing to practice medicine, nursing, and midwifery will diminish, and the burden of AIDS care will fall on already overcrowded, large urban hospitals. Blood transfusions will become unavailable because no one will want to be tested for HIV seropositivity. Xenophobia will characterize international relations, and governments will collapse, as educated decision-makers and managers die and cannot be replaced. The only bright spots in this otherwise dismal prospect are the increased awareness of young people of the need for chastity and monogamy, with an attendant fall in the level of sexually transmitted diseases generally; an acceleration in the development of health services and diagnostic facilities; the possibility of the development of a vaccine from the more benign HIV-2; a renewal of social life not based on sex; and a return to transcendental values and faith in God.^ieng

HIV infection in healthy persons in Uganda.

The results of several serological surveys, carried out in Uganda in the last 2 years, show that HIV infection is present in a number of different groups of individuals. There is a wide range of seropositivity (0 to 67.7%) seen within Uganda. In the sexually inactive, whether primary school pupils or residents of old people's homes, no serological evidence of HIV infection was found. In young adults in Kampala the HIV seropositivity ranged from 10.6 to 24.1%, whereas in rural adults the range was from 1.4 to 12.5%. Those with the greatest number of lifetime sexual partners had the highest rate of seropositivity, ranging from 32 to 67.7%. These rates are probably dependent on a number of factors, including sexuality.

PIP: Current levels of human immunodeficiency virus (HIV) infection in apparently healthy people in Uganda who represented groups considered to be at either high or low risk were examined through use of the competitive ELISA test. The following rates of seropositivity were recorded: barmaids (n=185), 67.7%; lorry drivers and turnboys (n=74), 32%; male blood donors (n=1370), 15%; female blood donors (n=214), 21%; sexual contacts of patients with AIDS (n=14), 71%; social contacts of AIDS patients (n=100), 2%; rural inhabitants of Mukono (n=289), 4.8%; rural inhabitants of West Nile (n=71), 1.4%; old people (n+96), 0%; and children (n=131), 0%. Among 1400 pregnant women tested in 3 areas, seroprevalence ranged from 10.6-24.1%. Overall, the highest rates of seroprevalence were found in those groups having the greatest numbers of sexual partners, e.g., barmaids or lorry drivers. This finding is consistent with the high rates of HIV infection recorded among prostitutes in neighboring African countries. Further evidence that HIV infection is associated with heterosexual activity is provided by the 71% seroprevalence rate among sexual partners of AIDS patients.

HIV infection through normal heterosexual contact in Uganda.

One hundred and fourteen household contacts of 23 patients with AIDS or suspected AIDS were examined for evidence of infection with HIV. In total 12 contacts had antibodies to the virus by a competitive enzyme-linked immunosorbent assay (ELISA), confirmed by Western blot. Ten of these seropositive contacts were the sexual partners of the index cases. Overall 71% of sexual partners (10:14) were seropositive. By contrast only 2:100 of the non-sexual contacts had evidence of infection. These were the daughter of an index case and her 2-year-old son who were seropositive but had their own independent risk factors. The data presented here support the hypothesis that a major route of transmission of HIV in an African population is through heterosexual contact and furthermore suggest that transmission by other means such as intimate non-sexual contact, insect vectors, or the use of non-sterile needles is much less important.

Enteropathic AIDS in Uganda. An endoscopic, histological and microbiological study.

Twenty-three Ugandan patients with enteropathic acquired immunodeficiency syndrome (AIDS, 'slim' disease) were studied. Upper gastrointestinal (GI) endoscopy, colonoscopy, biopsy, stool parasitology and culture were performed. Endoscopy revealed oral and/or oesophageal candidiasis in 22 patients. Stool examination and histology of the upper GI tract showed that 11 patients had cryptosporidiosis and three had isosporiasis (total of 61% of patients with coccidian enteritis). One case of possible Mycobacterium avium mycobacteriosis was also identified. Enteropathic AIDS in Uganda presents with a spectrum of infections similar to that found in developed countries, but the incidence of cryptosporidiosis and isosporiasis is higher.

PIP: Of about 40 patients with presumed enteropathic Acquired Immune Deficiency Syndrome (AIDS), i.e., oral thrush, diarrhea, and weight loss, admitted to Mulago Hospital medical wards, Uganda, from October through November 985, 23 patients were studied with upper gastrointestinal tract endoscopy and stool examination. Those patients chosen for study suffered with diarrhea, weight loss, and oral candidiasis and were willing to tolerate endoscopy. Weight loss was not quantified in most patients, but generally it was profound. 10 of the patients gave a history of genital sores or venereal disease. There were 16 males and 7 females with an age range of 19-47 years. All were sexually active, and all denied homosexuality anal intercourse, and intravenous drug abuse. 4 patients had had blood transfusion. The 23 patients represented a cross-section of the population with most social classes included. 20 patients were seropositive with antibody to HIV. Specimens from 2 patients were lost. 1 patient was seronegative. Apart from 5 patients who had been treated with nystatin for oral thrush and clinically presumed esophageal candidiasis, all the patients had oral thrush at the time of endoscopy. 20 patients had obvious esophageal candidiasis, and 1 patient had the appearance of Kaposi's sarcoma in the esophagus. Stool examination and histology of the upper GI tract showed that 11 patients had cryptosporidiosis and 3 had isosporiasis (total of 61% of patients with coccidian enteritis). 1 case of Mycobacterium avium mycobacteriosis also was identified. The incidence of cryptosporidiosis and isosporiasis is higher in Uganda than in developed countries.

How long has the AIDS virus been in Uganda?

PIP: In a study conducted in the 1970s, 66.7% of healthy Ugandan children living in the West Nile district tested positive for HIV infection by direct ELISA assay. But such assays frequently yield false-positive results when sera are tested from areas where parasitic infestation is common. This study attempts to determine how long the AIDS virus has been present among the Ugandan population through a re-examination of sera from the West Nile district and an examination of the sera of old people from the Kampala area. A competitive ELISA assay was used which does not have many of the drawbacks associated with direct ELISA assays. Of 71 healthy adults tested in the West Nile district, 1 tested positive for HIV infection. 15% of healthy adults in Kampala tested positive. Of 96 old people in Kampala, all of whom for various reasons were thought to have been sexually inactive for the past 5 years, none tested positive for HIV infection. The indications of this study are that AIDS is not endemic in the West Nile, and the disease is a recent arrival to Uganda. Previous suggestions that the disease originated in Uganda are incorrect.^ieng

Slim disease: a new disease in Uganda and its association with HTLV-III infection.

A new disease has recently been recognised in rural Uganda. Because the major symptoms are weight loss and diarrhoea, it is known locally as slim disease. It is strongly associated with HTLV-III infection (63 out of 71 patients) and affects females nearly as frequently as males. The clinical features are similar to those of enteropathic acquired immunodeficiency syndrome as seen in neighbouring Zaire. However, the syndrome is rarely associated with Kaposi's sarcoma (KS), although KS is endemic in this area of Uganda. Slim disease occurs predominantly in the heterosexually promiscuous population and there is no clear evidence to implicate other possible means of transmission, such as by insect vectors or re-used injection needles. The site and timing of the first reported cases suggest that the disease arose in Tanzania.

Multiple skin testing of tuberculosis patients with a range of new tuberculins, and a comparison with leprosy and Mycobacterium ulcerans infection.

Four hundred and seventy tuberculosis patients were each skin tested with four of a range of 17 mycobacterial reagents in four countries in all of which tuberculosis and leprosy were endemic. Sixteen of the reagents were new tuberculins prepared from extracts of living mycobacteria disrupted by ultrasonic disintegration and the last was PPD, RT23.The effect that tuberculosis exerted on the delayed-type skin test response to these antigens was assessed by comparing results for tuberculosis patients with those for Tuberculin positive and Tuberculin negative control populations. Tuberculosis patients on Rifampicin therapy showed no difference in their skin test responses to any of the antigens from those patients on other forms of antituberculosis treatment.Amongst the normal population it was found that possession of Tuberculin positivity was associated with an enhanced response to all the other mycobacterial antigens with the exception of A(*)-in which demonstrated a reciprocal relationship with Tuberculin in Burma. It was also noted, in Burma particularly, that sensitization to mycobacterial species other than Mycobacterium tuberculosis, especially to the slow growers, plays a role in determining responses to different mycobacterial species.In tuberculosis patients enhanced skin test responses were also seen but only in those countries, e.g. Libya, where the prevalence of mycobacterial species was low. Where mycobacteria were common, as in Burma, the converse was true and tuberculosis was associated with a diminished skin test response to each antigen. The high prevalence of A(*)-in positivity in Burma, its reciprocal relationship with Tuberculin there and the results for all the antigens in the tuberculosis patients indicate that the cell mediated skin test response may have a threshold. If this is exceeded the skin test becomes negative so that non-reactors then include those who have been excessively sensitized as well as those who have not been sensitized. Despite this, a greater percentage of tuberculosis patients in each country responded to the specific reagent Tuberculin than did the control populations and their mean positive induration sizes were consistently larger. Nevertheless, amongst the tuberculosis patients in Burma 13% were complete non-reactors to Tuberculin and this apparent anergy also applied to the other reagents with which these individuals were tested.This differs from lepromatous leprosy where the anergic state pertains exclusively to M. leprae and a few seemingly closely related species. The breadth of anergy in M. ulcerans infection has not been measured but it is known to effect both Burulin and the PPD, RT23.Just as in leprosy and M. ulcerans infection, tuberculosis can be shown to have a disease spectrum here detected by multiple skin testing. The significance of this spectrum and its similarities with and differences from that of the other mycobacterioses is discussed.

A study of alleged leprosy bacillus strain HI-75.

Subcultures of strain HI-75 of Skinsnes leprosy bacillus received in Antwerp and London have been studied bacteriologically and compared. Both contained moderately large acid-fast bacilli readily subcultured and maintained on ordinary mycobacteriologic media. These organisms were found to be a variety of Mycobacterium marianum (syn. serofulaceum) and were considered likely to be a laboratory contaminant. The earlier subculture studied also contained numbers of a much smaller mycobacterium (of a similar size to M. leprae) which appeared to be dead and which did not grow on the ordinary media. Skin tests and immunodiffusion analyses performed with extracts of the earlier subculture failed to demonstrate the presence of the specific antigens of leprosy bacilli. Similar studies on other cultures of Skinsnes bacillus must be performed to confirm or refute its identity as M. leprae.

Preliminary evidence for the trapping of antigen-specific lymphocytes in the lymphoid tissue of 'anergic' tuberculosis patients.

Lymphocyte-transformation responses to mycobacterial antigens have been studied, using paired blood and lymph node samples from 'normal' Ugandans, (hernia repairs or orthopaedic cases) or from patients with tuberculosis, Mycobacterium ulcerans infection, or injection abscesses. The results suggest that in some individuals, antigen reactive cells, although absent from the periphery, may be demonstrable in the lymph nodes. This phenomenon is most striking in skin-test negative tuberculosis patients.