Oishi Kazunori

Oishi, Kazunori

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Present Situation and Future Prospects of the Collaborative Studies in Uganda : Treatment of HIV/AIDS Associated Opportunistic Infections

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208 Trop. Med., 40 (4), 208-211, December, 1998Present Situation and Future Prospects of the CollaborativeStudies in Uganda: Treatment of HIV/AIDS AssociatedOpportunistic InfectionsKazunori OISHIDepartment of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, JapanINTRODUCTIONThe acquired immunodeficiency syndrome (AIDS) is caused by the human immuno-deficiency virus (HIV), a retrovirus that preferentially infects CD4 lymphocytes and lead toprofound deficit in cellular immunity. The present HIV epidemic in Uganda is as severe asanywhere in the world. Among the total population of twenty million people, approximatelytwo hundred people are estimated to be infected with HIV-1. This disease is, therefore,seriously affecting the Ugandan society. Compromised immunesystem renders HIV-infectedadults more susceptible to a wide variety of pathogens. The paptients with AIDS in Ugandaare highly associated with opportunistic infection such as tuberculosis (TB), cryptococcalmeningitis and others.We, the Department of Internal Medicine, exchanged the memorandomfor the col-laborative studies with Makerere University in 1991, because the Dean of the Faculty ofMedicine, Mekerere University in Uganda visited our institute in 1989 and strongly requestedfor cooperation on the HIV/AIDS related studies. We, therefore, started the collaborativestudies on AIDS-related opportunistic infections from 1993.The purpose of the collaborative studies is to support the diagnosis and treatment ofHIV/AIDS associated opportunistic infections in Mulago Hospital, Makerere University. Wehave already developed three projects on major opportunistic infections among HIV-infectedUgandan adult. First, we developed a study for cryptococcal meningitis in AIDS paptients.We, next, developed a study on the treatment of pulmonary tuberculosis in HIV-infectedpersons. Finally, we carried out a study on community-acquired pneumonia. Weintroduce thestudies on cryptococcal meningitis and community-acquired pneumonia.Diagnosis and treatment of cryptococcal meningitis in patients with AIDs inUgandaCryptococcal meningitis is the most commoninvasive fungal infection in patients withAIDS, occuring in up to 30% in sub-Saharan Africa. This disease is regarded as a life-threatening opportunistic infection particularly in Africa. Fluconazole, one of the recentlydeveloped triazole antifungal drugs, shows a promising effect in the treatment of cryptococcalmeningitis in patients with AIDS. To establish the easily-managed and cost-effective an-209ticryptococcal therapy for AIDS-associated cryptococcal meningitis in developing countries,this study was designed to compare the effects of treatment with low-dose oral fluconazoleand short-term flucytosine with that of fluconazole alone (1). This study was developed fromJanuary to December in 1994. HIV seropositive patients over 16 years old were enrolled, ifthey presented cryptococcal meningitis-like symptoms and positive for cryptococcal stainingor antigen in cerebrospinal fluid.30 of 58 patients were randomized to receive combination therapy, and 28 were ran-domized to receive fluconazole monotherapy. Before treatment, almost all of the patients hadheadache, described as severe by 91% of patients. Half of the patients showed decreasedconsciousness. With respect to opportunistic infections other than cryptococcal meningitis,oral candidiasis was most frequently observed in 69%, and pulmonary tuberculosis was di-agnosed in 9%. The mean CD4 and CDS peripheral blood counts were 77 and 208/m.arespectively. There was no significant differences with respect to demographic characteris-tics, laboratory values, or clinical symptoms and sign between the treatment group at base-line.Wecould evaluate the survival rate of 50 patients at the end point of primary therapyand maintenance therapy for six months (Figure 1). Ten out of 25 patients receiving themonotherapy with fluconazole died within two weeks after the initial therapy, and only nine100800Iccà"fcri§8£6040200FLCZ+5FC(n=25)FLCZ alone (n=25) "X30 60 90 120 150 180Days after Therapy*P < 0.05 ( Vs FLCZ alone)Figure 1. Survival of AIDS patients with cryptococcal meningitis duringoral fluconazole with or without flucytosine in Uganda FLCZ-fluconazole, 5FC; flucytosine.210of these patients (36%) survived for two months. In contrast, the combination therapyreduced the early deaths among these patients during the first two weeks, and 14 of 25patients assigned to the combination therapy survived the full two months of initial therapy.At the end of the primary and maintenance therapy for 6 months, the survival rate of 25patients receiving the combination therapy (32%) was significantly higher than that (12%) ofthe 25 patients assigned to the monotherapy. Despite the improved survival rate in patientsreceiving the combination therapy, the rate of positive cryptococcal cultures in cerebrospinalfluid remained high at 2 months and 6 months post-treatment, respectively. These data in-dicated that a large proportion of the patients had quiescent disease both at the end point ofprimary and maintenance therapy. No serious adverse effects were noted in any of the en-rolled patients during the primary or maintenance therapy.These data support that treatment with fluconazole is a cost-effective and safe regimenthat improve the quality of life for patients with associated cryptococcal meningitis in HIV-epidemic developing countries. We, however, have the following problems. First, we stillhave a high mortality despite oral anti-cryptococcal drugs. Second, the total management ofthe treatment for cryptococcal meningitis in AIDS patients is difficult. Third, it is expensiveto supply the adequate antifungal chemotherapy.Diagnosis and treatment of community-acquired pneumonia among UgandanadultsIn tropical and developing countries at least one third of deaths are due to pulmonaryinfections. Before the outbreak of HIV infection in Africa, Streptococcus pneumoniae (S. pneu-moniae) was reported to be only one predominant pathogen of acute pneumonia. However,clinical and microbilogical characteristics for community-acquirred pneumonia in HIV-seropositive patients in Africa have not fully investigated. In this study, we evaluated clinicaland microbiological features, and clinical effectiveness by ampicillin therapy for community-acquired pneumonia amongUgandan adults particularly in the respect to HIV infection (2).The study was done from 1996 to March 1998. Patients over 16 years old were enrolledif they were confirmed to have acute pneumonia by clinical symptoms and findings of chestradiograph. Quantitative culture method on rabbit blood agar and Gram's staining for freshlyexpectorated sputum was used for microbiological diagnosis.More interestingly, 72.5% of 91 patients with community acquired pneumonia were in-fected with HIV-1. Their mean CD4 peripheral-blood counts and CD4/CD8 ratio were 330/mm3and 0.48, and these were significantly lower than those in HIV-seronegative patients. Forseverity of community-acquired pneumonia, there was no difference in respiratory rates, pulseoxymetry oxygen saturation (Sp02), extent of pneumonia on chest radiograph, and other in-flammatory data between HIV-seropositive and HIV-seronegative patients at baseline.Causative pathogens were determined by sputum or blood samples in 45 cases. Similarpattern of causative respiratory pathogens were identified in both groups, and major patho-gens were S. pneumoniae, H. influenzae, Moraxella catarrhalis, Staphylococcus aureus andKlebsiella pneumoniae.Parental ampicillin therapy followed by oral amoxicillin for one weeks was given im-mediately after enrollment. Clinical effectiveness was evaluated by improvement of clinical211symptoms and signs, and laboratory markers, and chest radiographs. We found 15 cases offair and poor responders in HIV-seropositive individuals, while there was only one fairresponder in HIV-seronegative individuals. More importantly, the mean CD4 pepripheralblood cell counts in the fair and poor responders were lower than those in good responder inHIV-seropositive patients.These data support that a large part of patients with community-acquired pneumonia inUganda were infected with HIV-1. No difference of causative pathogens was noted betweenHIV-seropositive and HIV-seronegative patients. HIV-1 associated immune suppression ap-peared to decrease the clinical effectiveness of ampicillin therapy for community-acquiredpenumonia. These data indicate that bacteriological diagnosis and careful antibiotic therapyare required for patients with community-acquired pneumonia.Present situation of the collaborative studiesAs introduced here, we have successfully carried out collaborative studies on treatmentof HIV/AIDS related opportunistic infections during the last seven years. We feel that moretraining of physicians or technicians are necessary for the high quality studies. Although weobtained the meaningful results in our collaborative study, how the knowledges and ex-periences from these studies are utilized for the clinical practice in the study place?Nevertheless, the published data may attract the attention for researchers or cliniciansinside and outside of Uganda. These secondary benefits may increase global recognition ofmedical needs in specific area and may change the priorities of governmental agencies, asquoted in editorial response of a certain journal (1).Future prospects of the collaborative studiesWhat is the future prospects and the goal of our collaborative studies? Not only toproduce the data, but also to integrate the knowledge or technology into the training inspecial field of studies is important. Their knowledge and experiences could be utilized forfuture projects and clinical practice in Uganda. It is also possible to develop basic studies oninfectious diseases in tropical area in certain research center in Uganda.In summary,these processes of collaborative studies may produce fruitful results whichcontributes to the clinical practice in Uganda, and promote to obtain the government supportsfor specific infectious diseases.REFE RENCES1 ) Mayanjya, H., Oishi, K, Mitarai, S., Yamashita, H., Kisembo, N., Watanabe, K, Izumi,T., Ococi-Jungala. Augustine, K., Mugerwa, R., Nagatake, T., Matsumoto, K. Combina-tion therapy with fluconazole and flucytosine for cryptococcal meningitis in Ugandanpatients with AIDS. (1998) Clin Infect Dis. 26: 1362-1366.2 ) Yoshimine, H., Oishi, K., Mubiru, F., Nalwoga, H., Takahashi, H., Mugerwa, R.Nagatake, T. Diagnosis and treatment for community-acquired ppneumonia amongUgandan adults: Impact of HIV-infection. (1998) 12 th World AIDS Conference Genevap285.

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Present Situation and Future Prospects of the Collaborative Studies in Uganda : Treatment of HIV/AIDS Associated Opportunistic Infections

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