Hyperreactive malaria in expatriates returning from sub-Saharan Africa.

The extreme presentation of hyperreactive malaria is hyperreactive malarial splenomegaly syndrome (HMS). Some patients present with a less pronounced syndrome. To investigate whether the degree of splenomegaly correlates with the degree of immune stimulation, whether prophylaxis or recent treatment play a role, and whether short therapy alone is effective, we examined retrospectively the medical records of expatriates with exposure to P. falciparum who attended our outpatient department from 1986 to 1997, particularly subacute symptoms or signs, strongly elevated malarial antibodies and elevated total serum IgM. We analysed duration of stay, prophlyaxis intake, spleen size, serum IgM levels and response to antimalarial treatment. Serum IgM levels were significantly higher in patients with larger splenomegaly. The use of chloroquine alone as treatment for presumptive or proved malaria attacks was correlated with larger spleen size. Short adequate antimalarial therapy resulted in marked improvement or complete recovery. In nine patients the hyperreactive response reappeared after re-exposure, in four of them twice. We conclude that patients with subacute symptoms but without gross splenomegaly may have very high levels of IgM and malarial antibodies, and relapse on re-exposure, suggesting the existence of a variant of the hyperreactive malarial splenomegaly syndrome without gross splenomegaly.

Recurring aseptic meningitis after travel to the tropics: a case of Mollaret's meningitis? Case report with review of the literature.

Recurrent aseptic meningitis in a 35-year-old caucasian woman is described. She had many attacks over a period of 9 years. The first attack occurred after travel in the tropics. In spite of extensive examinations no cause could be found for the recurrent attacks. Both the clinical presentation and characteristics of the cerebrospinal fluid are compatible with the diagnosis of Mollaret's meningitis. There is no known cure for this condition, although colchicine and indomethacin have been mentioned to relieve symptoms. In our patient, a treatment with indomethacin during the last attack resulted in a clear and rapid improvement of symptoms. Since this episode only mild relapses have occurred, all of which responded well to the same treatment. This case highlights the long time span in which attacks of Mollaret's meningitis can occur, and the spectacular benefit of indomethacin.

AIDS-associated cryptococcal meningitis in Rwanda (1983-1992): epidemiologic and diagnostic features.

OBJECTIVES: to document the trend of AIDS-associated Cryptococcus neoformans meningitis (CM) in Kigali, Rwanda, during 1983-1992, and to highlight some diagnostic and epidemiological features of the disease. METHODS: during the study period, 3476 cerebrospinal fluid (CSF) specimens from 2824 adults (1578 men, 1246 women) were analysed in the Laboratory of Microbiology at the Centre Hospitalier de Kigali, Rwanda, Central Africa, using direct examination, culture and detection of the cryptococcal antigen (CrAg) in the CSF. RESULTS: CM was diagnosed among 549 (19%) patients (347 men, 202 women) and was by far the leading cause of meningitis before Neisseria meningitidis (n=115), Streptococcus pneumoniae (n=68), Mycobacterium tuberculosis (n=26). E. coli, Klebsiella pneumoniae, non-typhoid Salmonella (n=l5) and streptococci (n=4). The number of CM increased from one case in 1983 to 130 new cases in 1992. All 293 tested CM patients had HIV-1 antibodies. The male/female ratio declined from 3.31 during 1983-1987 to 1.58 during 1988-1992. CM showed a seasonal fluctuation, the highest number of infections being observed during the long rainy season. The sensitivity and specificity of the latex test for diagnosing CM was 98% and 99%, respectively. Cryptococcus neoformans var. gattii was cultured from eight (1.6%) of the 499 culture positive patients. CONCLUSION: CM is an important opportunistic infection among AIDS patients in Central Africa. It remains a problematic diagnosis in areas with limited diagnostic facilities.

The return of tuberculosis.

At the end of the 20th century, tuberculosis remains a major public health issue. In developing countries tuberculosis is a leading cause of morbidity and mortality, and the spread of the HIV epidemic contributes significantly to the worsening of the situation. Coinfection with tuberculosis and HIV results in special diagnostic and therapeutic problems and uses up larger amounts of medical resources in developing countries. Outbreaks of multidrug resistant tuberculosis (MDR-TB) were first reported from US-American centers caring for HIV patients, but have now been observed in many other countries. In Western Europe the tuberculosis epidemic is under control, but increasing incidence rates in migrants raise new problems in these countries. Tuberculosis is uncontrolled in large parts of the former Soviet Union due to the socio-economic break-down in these countries. Only rigorous infection control measures on a world-wide scale will prevent further detoriation of this situation. Therefore, the extension of surveillance systems, and sufficient funding for the prevention, diagnosis, and treatment of tuberculosis by national governments and international organizations are all urgently needed.

[Primary chemoprevention of tuberculosis in HIV-infected patients in non-industrialized countries]. / Chimioprophylaxie primaire de la tuberculose chez les personnes infectées par le VIH dans les pays non industrialisés.

In randomized placebo-controlled trials in Haïti, Zambia and Uganda, prophylactic use of isoniazid (INH) for 6 to 12 months reduced the annual incidence of tuberculosis in HIV-infected patients by more than 50 per cent. For several years, WHO, IUTATLD and CDC have recommended that HIV-positive patients testing positive in a PPD test should be treated with INH as a form of anti-tuberculosis chemoprophylaxis (ATC). Whilst these recommendations are easy to follow in industrialized countries, widespread use of ATC in developing countries remains problematic because: (i) It is unknown what proportion of patients are likely to be re-infected at the end of ATC in countries where TB is endemic; (ii) It is possible that resistant bacilli may be selected due to the incomplete exclusion from the ATC program of patients with active TB at enrollment; (iii) It is difficult to identify asymptomatic carriers of M. tuberculosis at enrollment; (iv) It is doubtful that all patients will comply with a treatment regime which lasts several months; (v) The cost of a widespread ATC program, whose full benefit remains to be evaluated, may be difficult to justify. This paper attempts to review these issues and demonstrates the need for more population-based clinical trials in the field.

HIV infection as a risk factor for septic arthritis.

We prospectively studied the demographics, the clinical and diagnostic features, the HIV-1 serostatus and the therapeutic response for all new patients with septic arthritis (SA) admitted to the Department of Internal Medicine of the Centre Hospitalier de Kigali, Rwanda, over a 19 month period. SA was diagnosed in 24 patients (10 male, 14 female), of whom 19 (79%) were HIV-1 seropositive (HIVpos). Gonococcal arthritis was found in four patients, all HIVpos. Non-gonococcal bacterial arthritis was established in 16 patients, of whom 13 were HIVpos. Causative organisms involved in this group and the corresponding HIV-1 serostatus of the patients were: Staphylococcus aureus: 4; 2 HIVpos. 2 HIVneg: Streptococcus pneumoniae: 4; 4 HIVpos; Salmonella group B: 2; 2 HIVpos; Streptococcus group D: 1; 1 HIVpos; Klebsiella pneumoniae: 1; 1 HIVpos; undetermined: 4; 3 HIVpos; 1 HIVneg. Tuberculous arthritis was presumed in four patients, of whom two were HIVpos. HIV-1-associated SA had a classical acute presentation and an overall good prognosis Compared to a control group consisting of hospitalized patients with malaria as the sole diagnosis, patients with SA were more likely to be infected with HIV-1 (P = 0.005, or 6.3; 95% CI 1.7 22.2). Prevalence rate estimates of SA among HIVpos and HIVneg patients were 0.5 and 0.25%, respectively (P = 0.38). We conclude that HIV-1 infection appears as a risk factor for SA among patients hospitalized at the Centre Hospitalier de Kigali, but that SA cannot be used as a predictor for HIV-1 infection for hospitalized patients. SA occurs infrequently and may present at any stage of HIV-1 infection.

Antiretroviral treatment in Africa.

PIP: Demand for treatment with antiretroviral (ARV) drugs increased in Africa in the wake of the July 1996 AIDS Conference in Vancouver, during which combination ARV treatment including protease inhibitors was shown to dramatically improve the quality and length of life for people with AIDS. However, 1 year after the Vancouver Conference, ARV drugs remain scarce in Africa. Most people treated with antivirals in Africa try to acquire their drugs by ordering them through friends outside Africa or by travelling to Europe or the US. ARV treatment is becoming more complicated and treatment strategies change rapidly. The imbalance between the high price of ARV treatment and the scarcity of resources, competing health care needs, and the continent's weak health care systems all impede the introduction of large-scale ARV treatment in Africa. Nonetheless, if neither governments, organizations, nor industry provide ARV, HIV-infected people, their families, and physicians may try to obtain them through informal channels. Poor quality ARV may then be procured, sold at extremely high prices, and inadequately administered. Indications for ARV treatment, indications of ARV as preventive therapy, and requirements to introduce ARV are discussed.^ieng

Chronic diarrhea among adults in Kigali, Rwanda: association with bacterial enteropathogens, rectocolonic inflammation, and human immunodeficiency virus infection.

One hundred patients with chronic diarrhea were seen in the Department of Internal Medicine at the Centre Hospitalier de Kigali, Rwanda; stool and/or rectal swab culture was performed for these patients, and they underwent rectoscopy and serological testing for human immunodeficiency virus type 1 (HIV-1). Enteropathogenic bacteria were isolated from 39 (39%) of the patients: Shigella species (22 of 100 patients tested), non-typhi Salmonella (11/100), Aeromonas species (5/60), and Campylobacter species (4/60). Rectocolitis was seen in 70 (70%) of the patients. HIV-1 antibodies were detected in 82 (94%) of 87 patients tested. Cytomegalovirus was not found in rectal biopsy specimens from 29 patients. Entamoeba histolytica was detected in two of 31 rectal smears. Idiopathic ulcerative colitis was diagnosed for two HIV-1-seropositive patients. One or more AIDS-defining diseases were found in 32 (32%) of the patients, and 72 (72%) fulfilled the World Health Organization's clinical case definition criteria for AIDS. Chronic diarrhea, as seen in a hospital setting in a region highly endemic for HIV-1 infection, is strongly associated with HIV-1 infection, with rectocolonic inflammation, and with infection due to enteropathogenic bacteria.

Four years of natural history of HIV-1 infection in african women: a prospective cohort study in Kigali (Rwanda), 1988-1993.

Clinical features and mortality due to human immunodeficiency virus type-1 (HIV-1) infection in women are described as part of a prospective 4-year cohort study on perinatal transmission of HIV in Kigali, Rwanda. Two hundred fifteen HIV-seropositive (HIV+) and 216 HIV-seronegative (HIV-) pregnant women were enrolled at delivery between November 1988 and June 1989. Clinical information collected during systematic quarterly examinations was compared. HIV antibody tests were performed at delivery and CD4/CD8 lymphocyte counts at 15 days' postpartum. HIV--women who seroconverted during the follow-up period were excluded from the analysis of the comparison group starting at the date of seroconversion. At enrollment, all HIV+ women were asymptomatic for acquired immune deficiency syndrome (AIDS). Incidence of tuberculosis was 2.9 per 100 women-years (WY) after 4 years of follow-up in HIV+ women versus 0.2 per 100 WY among HIV- women (relative risk, 18.2; 95% confidence interval 2.4-137.0). Among HIV+ women, the incidence of AIDS (World Health Organization clinical AIDS definition) was 3.5 per 100 WY. The mortality rate was 4.4 per 100 WY among HIV+ women versus 0.5 per 100 WY among HIV- women. Clinical AIDS was present in only half of the fatalities. Tuberculosis was a major cause of morbidity and mortality in these HIV+ African women. An early diagnosis and an appropriate treatment or prevention of tuberculosis should improve the quality of life of HIV-infected patients in Africa.

An etiologic study of hemoglobinuria and blackwater fever in the Kivu Mountains, Zaire.

Between January 1985 and March 1986, in the high altitude area of Kivu, Eastern Zaïre, 38 patients presenting with hemoglobinuria as main manifestation were investigated. Profound glucose-6-phosphate dehydrogenase deficiency was detected in 4 patients, leptospirosis in 2 and Hantaan virus infection in 2. Hemolysis was doubtful (haptoglobin > 40 mg/dl, Hemoglobin > 12 g/dl) in 2 patients. Other potential causes of hemoglobinuria such as hemoglobinopathy, toxic agents, infectious diseases or blood transfusion incompatibility were carefully screened and excluded. The syndrome observed in the remaining 28 cases was strongly suggestive of blackwater fever (BWF) as described in malaria patients by several authors under the french name "fièvre bilieuse hémoglobinurique". Quinine was used as curative treatment of malaria before admission in a significant greater proportion (p < 0.01) of patients with BWF compared to patients with uncomplicated malaria, suggesting that this drug might have played a triggering role in the genesis of BWF. However, quinine was usually administered at inadequate doses to malaria patients non responding to chloroquine and belonging to a population of whom 50% are non immune. It may thus also be hypothesized that BWF in our patients could result from a hyperparasitemic state that remained undetected because of an unusual synchronous lysis of infected erythrocytes. In the latter case BWF would correspond to a major complication of falciparum malaria only coincidentally related to the use of quinine.

Classification of HIV infection and disease in women from Rwanda. Evaluation of the World Health Organization HIV staging system and recommended modifications.

OBJECTIVE: To develop a human immunodeficiency virus (HIV) staging system for sub-Saharan Africa on the basis of an evaluation of the World Health Organization (WHO) system and predictors of mortality. DESIGN: Prospective cohort study with 4 years of follow-up. SETTING: Kigali, Rwanda. PATIENTS: 412 HIV-infected women recruited from prenatal and pediatric clinics. MEASUREMENTS: Clinical signs and symptoms of HIV disease, laboratory assays (including complete blood count and erythrocyte sedimentation rate), and cumulative mortality. RESULTS: The WHO staging system includes a clinical and a laboratory axis. The clinical axis was revised by inclusion of oral candidiasis, chronic oral or genital ulcers, and pulmonary tuberculosis as "severe" disease (clinical stage IV); in addition, body mass index was substituted for weight loss in the definition for the wasting syndrome. The 36-month cumulative mortality was 7% for women in modified clinical stage I ("asymptomatic"), 15% for those in stage II, 19% for those in stage III, and 36% for those in stage IV (P < 0.001). The laboratory axis was revised by replacing lymphocyte count with hematocrit and erythrocyte sedimentation rate. The 36-month mortality was 10% for women in modified stage A ("normal" laboratory results) and 33% for those in stage B (erythrocyte sedimentation rate > 65 mm/h or hematocrit < 0.38) (P < 0.001). A single staging system combining clinical and laboratory criteria is proposed, with a 36-month mortality of 7% for women in combined stage I, 10% for those in stage II, 29% for those in stage III, and 62% for those in stage IV (P < 0.001). CONCLUSIONS: On the basis of this analysis, a staging system relevant for sub-Saharan Africa is proposed that reflects the range of HIV-related outcomes, has strong prognostic significance, includes inexpensive and available laboratory tests, and can be used by both clinicians and researchers.

PIP: In Rwanda, health workers followed 412 HIV infected women attending prenatal and pediatric outpatient clinics in Kigali for 4 years. Researchers used these findings to evaluate WHO's HIV Staging System and predictors of mortality and to produce an HIV staging system for sub-Saharan Africa. The 36-month cumulative mortality was 9% for women originally in stage I, 15% for those in stage II, and 25% for those in stage III, and 27% for those in stage IV (p = 0.001). Significant predictors of mortality at 36 months were oral candidiasis, a low body mass index (=or 19 kg/sq. m), a history of oral or genital ulcers (especially chronic ulcers), a low hematocrit (0.38), and a high erythrocyte sedimentation rate (65 mm/h) (p 0.001). 12 of the 96 women who died by 36 months had developed pulmonary or extrapulmonary tuberculosis (TB). The researchers revised the WHO system by adding oral candidiasis, chronic oral or genital ulcers, and pulmonary TB to clinical stage IV (severe HIV disease). In the laboratory axis of the system, they replaced lymphocyte count with hematocrit and erythrocyte sedimentation rate. Using the modified laboratory axis, the 36-month mortality rate was 10% for women with normal laboratory results (stage A) and 33% for those with low hematocrit and a high erythrocyte sedimentation rate (stage B). Based on the proposed single staging system, the 36-month mortality rate was 7% for women in stage I, 10% for those in stage II, 29% for those in stage III, and 62% for those in stage IV (p 0.001). The researchers used these results to propose a staging system that is relevant for sub-Saharan Africa, considers the extent of HIV-related outcomes, requires only inexpensive and available laboratory tests, and has clear prognostic significance. Both clinicians and researchers can use this modified staging system.

Pulmonary cryptococcosis associated with HIV-1 infection in Rwanda: a retrospective study of 37 cases.

OBJECTIVES: To study the demographic, clinical, radiographic and diagnostic features, the clinical course and therapeutic response of pulmonary cryptococcosis in HIV-1-infected patients. DESIGN: Retrospective review. SETTING: The Department of Medicine of an urban reference hospital in Central Africa. METHODS: All the records of HIV-1-infected patients with pulmonary cryptococcosis were reviewed retrospectively with regard to the parameters described above. RESULTS: Over a 3-year period, pulmonary cryptococcosis was diagnosed in 37 HIV-1-infected Rwandan patients (21 men, 16 women; mean age, 35 years; range, 26-55 years). Twenty-nine patients (78%) had primary pulmonary cryptococcosis. Cough (94%), weight loss (65%), fever (51%), dyspnoea (46%), thoracic pain (30%), headache (13%) and haemoptysis (8%) were the predominant clinical findings. A diffuse interstitial infiltrate on chest radiograph was observed in 76% of the patients, an alveolar pattern in 19%, mediastinal and/or hilar adenopathy in 11%, nodules and pleural effusion each in 5%. Bronchoalveolar lavage, with a yield of 82%, was found to be the most sensitive diagnostic procedure. Screening of cryptococcal antigen in the serum failed to detect cases of primary pulmonary cryptococcosis. Twelve patients with primary pulmonary cryptococcosis treated with itraconazole as acute and maintenance therapy were all protected against disseminated cryptococcal disease; seven out of 10 (70%) of those who did not receive a specific anticryptococcal drug developed disseminated cryptococcal disease. CONCLUSION: Pulmonary cryptococcosis is not a rare complication of HIV-1 infection in Rwanda. Its clinical and radiographic patterns are non-specific and bronchoalveolar lavage is the procedure of choice for its diagnosis. The natural history of untreated primary pulmonary cryptococcosis is disseminated cryptococcal disease. Itraconazole is highly effective in the prevention of disseminated cryptococcal disease in patients with primary pulmonary cryptococcosis.

Pulmonary disease associated with the human immunodeficiency virus in Kigali, Rwanda. A fiberoptic bronchoscopic study of 111 cases of undetermined etiology.

All human immunodeficiency virus type 1 (HIV-1) infected adult patients referred to the Division of Pulmonary Diseases of the Centre Hospitalier de Kigali, Rwanda for evaluation of a pulmonary disease of undetermined etiology (PDUE) were investigated by fiberoptic bronchoscopy using both bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB). During a 10-mo period 111 HIV-1 infected patients with PDUE were examined, of whom 47 (42%) fulfilled the World Health Organization (WHO) clinical case definition for acquired immunodeficiency syndrome (AIDS) and seven (6%) had an AIDS-defining illness. Nonspecific interstitial pneumonitis was diagnosed in 42 (38%) patients, tuberculosis in 25 (23%), cryptococcosis in 14 (13%), Kaposi's sarcoma (KS) in 10 (9%), Pneumocystis carinii pneumonia (PCP) in five (5%). The diagnosis remained undetermined in 18 (16%) patients. Chest radiograph patterns were generally nonspecific. TBB and BAL had diagnostic yields of 82 and 26% of all final diagnoses, respectively. Our study on Rwandese HIV-1-infected patients with PDUE provides evidence for a large spectrum of pulmonary diseases with relative frequencies differing strikingly from those in developed countries. Detailed investigations confirm the rarity of PCP in Africa and highlight nonspecific interstitial pneumonitis as the predominant diagnosis of PDUE. Empiric antituberculosis treatment is justified in the absence of clinical manifestations suggestive of a specific diagnosis and while awaiting the results of the diagnostic procedures. Primary prophylaxis for PCP would not be appropriate in Africa.