Treatment Discontinuation in Adult HIV-Infected Patients on First-Line Antiretroviral Therapy in Nigeria.

BACKGROUND: Retention in care and treatment services is critical to health outcomes of individuals diagnosed and living with HIV. We evaluated the incidence of and risk factors for treatment discontinuation (TD) in a large adult HIV population on ART in Nigeria. METHOD: A retrospective cohort study of adult HIV patients initiated on first-line ART between 2004 and 2011 at the Jos University Teaching Hospital (JUTH) in Nigeria. Follow up information of participants was retrieved from various sources (patient visit database, pharmacy data and patients charts) up to the end of 2012. The primary study endpoint was TD, defined as discontinuation of ART for any reason, including death or loss to follow-up (lack of pharmacy pick-up for periods≥12 months). The Incidence and hazard for TD were estimated by Kaplan-Meier and Cox proportional regression analysis, respectively. RESULT: Overall, 3,362 (28%) patients discontinued treatment during 49,436 person-years (py) of follow-up (incidence rate (IR) 6.8 TD per 100 py). The hazard of treatment discontinuation decreased with increasing age (adjusted hazard ratio (aHR 0.99; 95% CI 0.98-0.99). Other independent risk factors for treatment discontinuation were: being unmarried (aHR 1.24; 95% CI: 1.12-1.38), having primary or secondary level of education as compared to tertiary level education (aHR 1.24; 95% CI: 1.12-1.40) and average percent adherence to drug refill visits<95% (adjusted hazard ratio (aHR) 2.13; 95% CI: 1.9-2.40). Compared to tenofovir, greater hazard of TD was noted in patients initiated on ART containing didanosine (aHR) 1.73; 95% CI: 1.03-2.91), but lower in those initiated on zidovudine containing regimen (aHR 0.77; 95% CI: 0.69-0.86). CONCLUSION: Long-term treatment discontinuation rate in this study was comparable to estimates in resource-rich countries. Younger patients, as well as patients with lower educational levels and those with poor adherence had significant hazards for treatment discontinuation and should be the target of interventions to reduce treatment discontinuation and improve retention, especially within the first year of ART.

Patients who present late to HIV care and associated risk factors in Nigeria.

OBJECTIVES: Our objectives were to assess trends in late presentation and advanced HIV disease (AHD) and determine associated risk factors. METHODS: We conducted a retrospective cohort analysis of patients who had received care and treatment at the AIDS Prevention Initiative Nigeria Plus (APIN)/Harvard School of Public Health-President's Emergency Plan for AIDS Relief (PEPFAR) programme at the Jos University Teaching Hospital, Jos, Nigeria from 2005 to 2010. We used the European Consensus Definition to assess trends in late presentation (CD4 count < 350 cells/µL or AIDS-defining illness) and AHD (CD4 count < 200 cells/µL or AIDS-defining illness) and evaluated associated risk factors using logistic regression methods. RESULTS: Among 14,487 eligible patients, 12,401 (85.6%) were late presenters and 9127 (63.0%) presented with AHD. Late presentation decreased from 88.9% in 2005 to 80.1% in 2010 (P < 0.001). Similarly, AHD decreased from 67.8% in 2005 to 53.6% in 2010 (P < 0.001). In logistic regression models adjusting for sociodemographic and biological variables, male sex [adjusted odds ratio (aOR) = 1.80; 95% confidence interval (CI) 1.60-2.04], older age (aOR = 1.37; 95% CI 1.22-1.54), civil service employment (aOR = 1.48; 95% CI 1.00-2.21), referral from out-patient (aOR = 2.18; 95% CI 1.53-3.08) and in-patient (aOR = 1.55; 95% CI 1.11-2.17) services, and hepatitis B virus (aOR = 1.43; 95% CI 1.26-1.63) and hepatitis C virus (aOR = 1.18; 95% CI 1.02-1.37) coinfections were associated with late presentation. Predictors of AHD were male sex (aOR = 1.67; 95% CI 1.54-1.82), older age (aOR = 1.26; 95% CI 1.16-1.36), unemployment (aOR = 1.34; 95% CI 1.00-1.79), referral from out-patient (aOR = 2.40; 95% CI 1.84-3.14) and in-patient (aOR = 1.97; 95% CI 1.51-2.57) services and hepatitis B virus coinfection (aOR = 1.30; 95% CI 1.19-1.42). CONCLUSIONS: Efforts to reduce the proportion of patients who first seek care at late stages of disease are needed. The identified risk factors should be utilized in formulating targeted public health interventions to improve early diagnosis and presentation for HIV care.

Temporal changes in renal glomerular function associated with the use of Tenofovir Disoproxil Fumarate in HIV-infected Nigerians.

BACKGROUND: Reports of renal dysfunction in Tenofovir Disoproxil Fumarate (TDF)-treated HIV-1 infected patients have raised concerns about potential nephrotoxicity. OBJECTIVE: To compare the effects on renal function of TDF-containing highly active anti-retroviral therapy (HAART) with a non-TDF-containing HAART. METHODS: This was an observational study.Clinical and laboratory data of 186 HIV-1 infected adult Nigerians on first-line HAART for at least 48 weeks were reviewed. Eighty-four patients whose nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone included TDF were compared to 102 patients on other NRTI backbones. Creatinine clearance (CLcr) was estimated using the Cockcroft-Gault equation. Changes in serum creatinine and CLcr from the baseline for each patient were compared between the TDF-treated and the TDF-free patients. We also assessed the associations of other variables with change in CLcr... RESULTS: Baseline median serum creatinine (mmol/L) was 77 and 84 in the TDF-treated and TDF-free groups, respectively (p=0.59). Baseline median CLcr (mls/min) was 83 in the TDF-treated patients vs 78 in the TDF-free group. At 48 weeks, serum creatinine increased by 18.1% and 1.2% in the TDF-treated and TDF-free arms, respectively. There was a decrease of 4.8% in GFR in the TDF arm compared to a gain 5.1% in the TDF-free arm. CONCLUSION: Tenofovir Disoproxil Fumarate-containing HAART is associated with a slight decline in the medium term in CLcr compared with HAART regimens containing alternative Nucleosid(t) Reverse Transcriptase Inhibitors.

Frequency of cryptococcal meningitis in HIV-1 infected patients in north central Nigeria.

BACKGROUND: Cryptococcal meningitis (CM) is the most common severe life threatening fungal infection in AIDS patients. It is an important cause of morbidity and mortality There is paucity of data on the prevalence of CM in Nigeria. We aimed to determine the frequency of CM, the clinical presentation and immunological profile. METHODS: A cross sectional study was carried out at the Jos University Teaching Hospital (JUTH). A total of 100 HIV-1 infected patients suspected of having meningitis or meningoencephalitis were subjected to cerebrospinal fluid (CSF) analysis (including Indian ink preparation and fungal culture by conventional methods) and CD4 count was determined using flow cytometry (count bit Y-R 1004 Partec Muster Germany). RESULTS: The freguency of CM was 36% in our cohort. The commonest clinical presentation included headache (100.0%), neck stiffness (77.8%), fever (72.0%), vomiting 55.6%), personality changes (55.6%), photophobia (27.8%) and convulsions (27.8%). The mean duration of symptoms was 24 +/- 22 days with a median of 17 days. The mean CD4 count was 89 +/- 60 cells/mm3 with a median of 82 cells/mm3. CONCLUSION: The high prevalence of CM and the associated severe immunosuppression underscores the importance of early diagnosis of HIV infection which may reduce the incidence of CM. There is the urgent need for access to Amphotericin B and fluconazole in resource constrained settings in addition to a wide access to HAART.

Presentation and survival of patients with AIDS-related Kaposi's sarcoma in Jos, Nigeria.

AIDS-related Kaposi's sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe the pattern of presentation and survival in Jos, Nigeria. We identified 48 HIV-positive patients with AIDS-KS and matched them for age and sex with an equal number of HIV-positive patients without AIDS-KS. We compared their clinical, immunological, virological characteristics and survival. They were similar in age and body mass index profile but patients with AIDS-KS had more tuberculosis co-infection (P, 0.02), lower median CD4 count (P, 0.003) and higher mortality (P, 0.002). Surprisingly, patients with AIDS-KS had lower levels of median viral load (29,347 copies/mL) compared with controls (80,533 copies/mL). We recommend specific AIDS-KS therapy in addition to highly active antiretroviral therapy in order to improve survival.

The clinical features of HIV/AIDS at presentation at the Jos University Teaching Hospital.

BACKGROUND: The clinical characteristics and consequences of HIV-I infection observed in studies from developed countries cannot be generalized across the multiple virus subtypes that circulate in sub-Saharan Africa in general and Nigeria in particular. This study was therefore conducted to determine the commonest symptoms and signs at presentation in HIV-infected individuals at the Jos University Teaching Hospital. METHOD: This descriptive study was conducted at the antiretroviral clinic of the Jos University Teaching Hospital, Jos, between May and October 2004. Two hundred (200) newly diagnosed and laboratory confirmed adult cases of HIV infection without prior antiretroviral drug use were recruited after obtaining informed consent. Each qualified patient had a comprehensive history taken with emphasis on the clinical symptoms and detailed physical examination performed by the researchers. The data collected were analyzed using a multipurpose computer programme, Epi-info 2000 version 1.1.3 (Atlanta GA, USA). RESULTS: There were 86 (43.0%) males and 114 (57.0%) females whose mean ages were 39.0 +/- 7.8 and 32.0 +/- 8.1 years, respectively. The major symptoms in the study population were: weight loss (65.5%), fever (41.5%), chronic cough (38.5%), diarrhea (32.0%), pruritus (13.0%) and body rash (12.5%). The major signs were pallor (25.0%), oral thrush (20.5%), wasting (20.0%), lymphadenopathy (18.0%), dermatitis (16.0%), hyperpigmented nails (13.5%) and finger clubbing (8.5%). CONCLUSION: The symptoms and signs of HIV/AIDS obtained were similar to those obtained by other workers from different parts of the world; however, the findings of hyperpigmented nails and finger clubbing have not been frequently reported for other populations.

The Clinical Features of HIV/AIDS at Presentation at the Jos University Teaching Hospital

Background: The clinical characteristics and consequences of HIV-1 infection observed in studies from developed countries cannot be generalized across the multiple virus subtypes that circulate in sub-Saharan Africa in general and Nigeria in particular. This study was therefore conducted to determine the commonest symptoms and signs at presentation in HIV-infected individuals at the Jos University Teaching Hospital.Method: This descriptive study was conducted at the antiretroviral clinic of the Jos University Teaching Hospital, Jos, between May and October 2004. Two hundred (200) newly diagnosed and laboratory confirmed adult cases of HIV infection without prior antiretroviral drug use were recruited after obtaining informed consent. Each qualified patient had a comprehensive history taken with emphasis on the clinical symptoms and detailed physical examination performed by the researchers. The data collected were analyzed using a multipurpose computer programme, Epi-info 2000 version 1.1.3 (Atlanta GA, USA). Results: There were 86(43.0%) males and 114(57.0%) females whose mean ages were 39.0±7.8 and 32.0±8.1 years, respectively. The major symptoms in the study population were: weight loss (65.5%), fever (41.5%), chronic cough (38.5%), diarrhea (32.0%), pruritus (13.0%) and body rash (12.5%). The major signs were pallor (25.0%), oral thrush (20.5%), wasting (20.0%), lymphadenopathy (18.0%), dermatitis (16.0%), hyperpigmented nails (13.5%) and finger clubbing (8.5%).Conclusion: The symptoms and signs of HIV/AIDS obtained were similar to those obtained by other workers from different parts of the world; however, the findings of hyperpigmented nails and finger clubbing have not been frequently reported for other populations

Direct observation therapy-highly active antiretroviral therapy in a resource-limited setting: the use of community treatment support can be effective.

This study examines the use of various direct observation therapy-HAART treatment support modalities in Jos, Nigeria. A 12-month observational study enrolling 175 antiretroviral naïve patients into four arms of direct observation therapy-HAART (highly active antiretroviral therapy); daily observed therapy (DOT), twice weekly observed therapy (TWOT), weekly observed therapy (WOT) and self-administered therapy (SAT), examined community treatment support using family and community members. Treatment outcomes were much better in the treatment-supported groups compared with the control self-therapy group. CD4 cell increases were 218/microL (DOT), 267/microL (TWOT), 205/microL (WOT) versus 224/microL (SAT), whereas plasma HIV-1 RNA reached undetectable levels (<400 copies/mL) in 91%, 88%, 84% versus 79% of patients in the DOT, TWOT, WOT versus SAT groups, respectively, at 48 weeks. We, therefore, strongly support the use of treatment support in our settings.

Partner disclosure of HIV status among HIV positive mothers in Northern Nigeria.

Partner consent and support can substantially enhance adherence to PMTCT interventions. This study explores the issues concerning disclosure of HIV status to partners of HIV sero-positive mothers in a PMTCT programme in Jos, Northern Nigeria. Previously field-tested questionnaires were administered by trained counsellors to 570 consenting HIV positive mothers who were participating in the PMTCT programme at Jos University Teaching Hospital (JUTH), Jos. The findings were entered into Epi Info and analysed using frequencies. The median age of respondents was 29 years while that of their partners was 37 years. Five hundred and fifty-five (99.5%) of respondents were married. Majority of the women were Christians (82.9%) while 16.9% were Moslems. Seventy four percent (419/563) of the mothers were aware of their husband's HIV sero-status. Of these, 65.4% (274/419) of the partners were HIV positive while 34.6% were sero-negative. Eighty nine percent (500/560) of the women have disclosed their HIV status to their partners. Of these, 39.6% (199/502) required the assistance of health workers while 59.4% (298/502) did it by themselves. Following disclosure of HIV status, 86.9% (430/495) of the partners were supportive, 5.7% were indifferent, 6.7% were quarrelsome and abusive while 1.0% was violent. The reactions of partners of HIV positive mothers to disclosure of their wives' HIV status are predominantly supportive. This should strengthen strategies to promote partner disclosure.

CD4+ T-lymphocyte counts in patients with human immunodeficiency virus type 1 (HIV-1) and healthy population in Jos, Nigeria.

This study was undertaken to establish local CD4+LC standards, which could be used as indicators of immune deficiency or monitor progress of HIV therapy, instead of relying on Caucasian standards, which may not exactly reflect Nigerian CD4+LC sub-populations. CD4+LC from 1232 Nigerian adults were studied. They included 852 apparently healthy individuals, 172 HIV-positive persons with no major AIDS defining illnesses (AIDSDIL) and 208 HIV infected individuals with AIDSDIL. The mean CD4+LC of healthy Nigerians (821 +/- 12) was more than two times higher than the mean CD4+LC of HIV-positive individuals without AIDSDIL (369 +/- 14) and almost five times higher than the mean of HIV-positive individuals with AIDSDIL (163 +/- 13) (p < 0.05). In addition, a CD4+LC of < 200 cells/uL can be considered as an AIDS defining laboratory criterion in Nigerians as the 208 individuals with AIDSDIL had a mean CD4+LC of 163 cells/uL. This study therefore establishes a local standard range for CD4+LC in healthy and HIV infected Nigerians which can serve as reliable indices for HIV induced immune impairment and for monitoring effectiveness of HIV therapy.

Renal disease in the acquired immunodeficiency syndrome in north central Nigeria.

BACKGROUND: The brunt of the human immunodeficiency virus infection/the acquired immunodeficiency syndrome is largely borne by communities in sub-Saharan Africa. We describe renal disease in Nigerians with the acquired immunodeficiency syndrome. METHODS: Consecutive patients with the acquired immunodeficiency syndrome (AIDS) seen in the infections unit of the Jos University Teaching Hospital and a similar group of healthy controls were evaluated for renal disease. Subjects with past history of renal disease, hypovolemia, hypertension, diabetes mellitus and/or a documented fever were excluded from the study. RESULTS: Of the 79 patients with the acquired immunodeficiency syndrome and 57 controls studied, renal disease was present in 41 (51.8%) of the patients in the AIDS group and 7 (12.2%) of controls. While 15 (19%) of the AIDS group had azotemia alone and 20 (25.3%) had proteinuria alone, 6 (7.6%) had azotemia and proteinuria. The mean protein excretion/24 hours was significantly higher in the AIDS group compared to controls, (2.99 +/- 54 g and 0.56 +/- 0.12 g respectively, p = 0.001), while the GFR was significantly higher in controls compared to the study group (103.30 +/- 37.78 and 68.03 +/- 37.55 respectively, p = 0.004). Subjects in the AIDS group with renal disease had a significantly longer duration of illness compared to those without (12.33 +/- 8.67 months and 7.28 +/- 7.78 months respectively, p = 0.008). Age and serum CD4+ cell counts were similar in patients with and without renal disease in the AIDS group. CONCLUSION: Renal disease is a common complication of acquired immunodeficiency syndrome, the duration of illness being strongly associated with its presence.

A multicentre study to determine the efficacy and tolerability of a combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the treatment of HIV infected Nigerian patients.

Summary Forty (40) HIV positive patients with CD4 cell counts between 100 - 500 cellh/mm3 were recruited from 8 different centres in Nigeria including a research centre and specialist and teaching hospitaLs They were enrolled into an open, non-comparative study of a triple combination regimen containing the Protease Inhibitor (PI), Nelfinavir and two Reverse Transcriptase Inhibitors (RTIs), Zakitabine (Hivid) and Zidovudine for a period of 24 weeks. Thirty-one (31) patients completed the study. Nine (9) patients withdrew from the study. Two of these because of Adverse Events (AE), 2 others because they developed tuberculosis and had to withdraw because of rifampicin therapy. The remaining five (5), withdrew voluntarily. Efficacy of the PI containing triple regimen was evaluated using viral load and absolute CD4 changes, weight gain and clinical response during the course of the triaL Twenty-two (22) patients had plasma viral loads measured at the beginning and at the end of the trial (24 weeks). Seventeen (17) out of the 22 patients (77%), experienced a significant reduction in their plasma viral loads (p<0.05 There was 1 log reduction in plasma viral load in 6 patients (25%), 2 log in 4 patients (17%). In 2 patients (8%), plasma viral load was reduced below the level of detection. The viral load increased over the treatment period in five patients (21%). Similarly 22 out of the 26 patients (85%) experienced increase in the level of their CD4 lymphocyte counts at the end of the study. The average CD4 counts of all 26 patients rose from 272.94 +/- 137.71/dl to 414 +/- 243.71/ul over 24 weeks (p<0.05). There was monthly rise of 27 CD4 cells/microl. Four (4) patients (15%) had a fall in their CD4 lymphocyte counts. Twenty (20) out of the 26 patients (77%), who completed the study were observed to have weight gains ranging from 1.5 to 31 kilograms over the 24 week study period. In 4 patients, there was no weight gain during the study period. Two patients (5%) were withdrawn due to adverse events from the viracept combination. One of these was because of life threatening diarrhoea while the other patient had severe peripheral neuropathy and severe weakness in the lower limbs. Eight (8) other patients had diarrhoea but not severe enough to stop them from continuing with the triaL Other adverse events seen include anaemia (1 patient), pancytopenia (1 patient), and transient elevation of serum urea and creatinine (1 patient). None of these adverse events was severe enough to warrant withdrawal from therapy. The study has therefore demonstrated the significant efficacy and tolerability of (Nelfinavir/Zalcitabine/ Zidovudine combination in suppressing viral replication, increasing the CD4 cell counts and improving the quality of life in Nigeria patients with HIV.

Carriage rate of hepatitis-B surface antigen (HBsAg) in an urban community in Jos, Plateau State, Nigeria.

The carriage rate of Hepatitis-B surface antigen (HBsAg) in an urban community in Jos, the Plateau State capital, was studied to obtain the pattern of Hepatitis-beta virus (HBV) spread within the community. HBsAg screening was performed on a consecutive sample of 524 apparently healthy individuals (293 males and 231 females) aged 15-65 years who voluntarily turned up for the survey. Fifty-four (10.3%) were HBsAg positive by ELISA. The carriage rate in females 30/231 (13.0%) was significantly higher than in the males 24/293 (8.2%) (p<0.05). In relation to age, 14/144 (9.7%) were aged <20 years, 11/121 (9.1%) were 21-30 years, 7/115 (6.1%) were 31-40 years, 14/89 (15.7%) were 41-50 years, 2/27 (7.4%) were 51-60 years and 6/28 (21.4%) were >61 years. In relation to marital status, carriage rate was highest among the divorced/widowed group (12.5%) followed by the married group (10.6%). Carriage rates in relation to occupation showed that infection was highest among traders (13.7%) and students (13.2%). The survey therefore confirms the endemicity of HBV infection in Jos and describes the groups that are at risk. This calls for health education of the general population on preventive measures to check the spread of the virus in the community.

Genetic variability of HIV-1 protease from Nigeria and correlation with protease inhibitors drug resistance.

In Nigeria, the most populous country in Africa, the characterization of HIV-1 strains has been limited. In this study we evaluated the genetic diversity of the protease coding region, one of the anti-retroviral therapy target, and investigated the presence of mutations related to resistance to HIV protease inhibitors. We analyzed samples collected during 1996 and all patients were anti-retroviral drug naïves. Ten samples were evaluated by sequencing of the protease gene. The majority, 80%, were classified as subtype A and the two others were unclassified-divergent strains, something in between A and G subtypes. The gag region from these outliners were sequenced and the phylogenetic analysis classified them as subtype G. The protease amino acid consensus sequence of the Nigerian subtype A are in complete agreement with the consensus A differing from the USA subtype B consensus in 10 positions (L10V, I13V, K14R, I15V, K20I, M36I, R41K, P63L, H69K and L89M). The secondary substitutions associated with protease inhibitor resistance were observed in all Nigerian sequences at the positions L10V, M36I and L89M. The majority of sequence variation was concentrated in the interval between aminoacids 70-90 where the protease substrate binding region is located.

Clinical pattern of human immunodeficiency virus infection (HIV) in pulmonary tuberculosis patients in Jos, Nigeria.

A study of determine the seroprevalence rate and clinical presentation of HIV-associated pulmonary tuberculosis was carried out in Jos between October 1990 and September 1991. Out of the 180 newly diagnosed pulmonary tuberculosis patients, 11(6.1%) were confirmed seropositive for HIV-1 and 2. The peak age range for both tuberculosis and HIV infection in both sexes is 20-40 years. The risk of HIV infection was associated with multiple sex partners and blood transfusion. There was no significant difference in the clinical presentation of pulmonary tuberculosis between HIV-seropositive and seronegative patients (P > 0.1). However, diarrhoea, lymphadenopathy and marked weight loss were found to be significantly associated with HIV infection (P < 0.05). The mean lymphocyte count of HIV seropositives was significantly lower than seronegatives (P < 0.01).

PIP: While tuberculosis (TB) is already a highly common disease in developing countries, the advent and spread of HIV/AIDS has further increased the incidence of TB worldwide, especially in Africa. Findings are presented from a study conducted to determine the seroprevalence rate and clinical presentation of HIV-associated pulmonary TB among 180 newly diagnosed pulmonary TB patients at Jos University Teaching Hospital, Nigeria, between October 1990 and September 1991. 11 (6.1%) patients were confirmed seropositive for HIV-1 and HIV-2 infection, with the peak age range for both TB and HIV infection in both sexes being 20-40 years. The risk of HIV infection was associated with multiple sex partners and blood transfusion. No significant difference was observed in the clinical presentation of pulmonary TB between HIV-seropositive and seronegative patients. However, diarrhea, marked weight loss, and lymphadenopathy were significantly associated with HIV infection. The mean lymphocyte count of HIV seropositive individuals was significantly lower than among seronegative individuals.

Open clinical trial of roxithromycin amongst patients of Jos University Teaching Hospital with lower and upper respiratory tract infections.

An open non-comparative clinical study to determine the efficacy and tolerance of Roxithromycin 150 mg twice daily was carried out amongst Nigerian patients with acute upper and lower respiratory tract infections. Twenty-four (24) patients (mean age 21.6 years, male 13; females 11 who completed the study presented with acute tonsillitis (33.3%, acute bronchitis (12.5%), lober pneumonia (12.5%), Otitis media (8%), acute pharyngitis (4%) and acute sinusitis (4%). Most of the patients had normal bacterial flora isolated (50.3%). Pathogens isolated included streptococcus pyogenes (21%), moraxella catarhalis (8.3%), streptococcus pneumonia (8.3%) and Klebsiella pneumonia (4%). The quick clinical response, lack of major adverse drug reactions and susceptibility of the bacterial isolates to Roxithromycin were very significant attributes of the drug. In addition, there was complete recovery in 95.8% of the patients. Roxithromycin is therefore a well tolerated and effective drug for the treatment of acute respiratory tract infections in Nigerian patients.

Zinc status in chronic liver disease; studies in Nigerian patients.

Serum and urinary zinc were assessed in 53 patients with a variety of chronic liver diseases (CLD) and 59 healthy volunteers using atomic absorption spectrophotometry. Liver zinc was also assessed in 18 patients and 10 controls. All patients had significantly lower serum zinc (mean = 36.3 +/- 2.9 ug/dl) than controls (79.3 +/- 4.0 ug/dl) and higher urinary excretion (651.0 +/- 53 ug/24 hrs) than controls (316.0 +/- 26 ug/24 hrs). Mean liver zinc was also lower in cirrhotic patients (85.10 +/- 21.31 ug/g) than control values (112.40 +/- 31.72 ug/g) but patients with schistosomiasis had identical values with controls. Decreasing levels were noted from chronic hepatitis through cirrhosis to primary liver cancer and decompensated patients had lower levels than well-compensated disease. No difference was seen between alcoholic and non-alcoholic cirrhotics. This study indicates that hyperzincuria occurs in association with zinc deficiency in CLD, an abnormality which may be important in the genesis of some features of the disease.

Cerebrospinal fluid changes in tetanus: raised proteins and immunoglobulins in patients with severe disease.

34 patients with tetanus were studied; all had normal serum proteins and albumin. Only 3 samples of cerebrospinal fluid (CSF) contained cells (a few polymorphonuclear leucocytes). Protein levels in the CSF were elevated in 26 patients (76.5%); 11 cases with clinically mild tetanus had a mean CSF protein of 400 +/- 250 mg/litre (normal 100-400 mg/litre), while the CSF protein levels of 10 patients who died (mean 1596 +/- 985 mg/litre; P less than 0.005) and those of 4 others with severe disease who absconded were much higher (mean 1220 +/- 562 mg/litre; P less than 0.005). As a group, 19 patients with severe disease including the 10 fatal cases also had significantly higher mean CSF protein values (1582 +/- 938 mg/litre; P less than 0.005) than did the mild cases. Immunochemical analysis of the proteins using a radial immunodiffusion assay showed that these proteins were immunoglobulin G (IgG). Polyacrylamide gel electrophoresis demonstrated an oligoclonal gammaglobulin pattern, suggesting intrathecal IgG synthesis in these patients. These studies suggest that measurement of CSF proteins may supplement clinical evaluation in tetanus and that there may be a local immune stimulus (perhaps a tetanus antigen or to some other mitogen) in the central nervous system.