HIV co-infection with tuberculous and non-tuberculous mycobacteria in western Kenya: challenges in the diagnosis and management.

BACKGROUND: Tuberculosis (TB) and HIV co-infections have a global prevalence with devastating morbidity and massive mortality, Sub-Saharan Africa being the worst hit. OBJECTIVES: To evaluate the prevalence of TB-HIV co-infection and demonstrate the confusion caused by NTM and HIV/AIDS co-infection in TB diagnosis and treatment in western Kenya. METHODS: In a cross-sectional study carried out at 10 hospitals in western Kenya, sputa from consenting 872 TB suspects underwent microscopy, and culture on Lowenstein-Jensen and Mycobacteria Growth Index Tube media. Isolates were identified using the Hain's GenoType(®) Mycobacterium CM and GenoType(®) Mycobacterium AS kits. A total of 695 participants were screened for HIV using Uni-Gold™ test and positives confirmed with the enzyme linked immunosorbent assay. RESULTS: A total of 346 (39.7%) participants were diagnosed with TB. Out of the 346 TB cases, 263 (76%) were tested for HIV infection and 110 (41.8%) of these were sero-positive (co-infected). The female to male TB-HIV co-infection prevalence ratio (PR) was 1.35. This study reports isolation of non-tuberculous mycobacteria from TB suspects at a rate of 1.7%. CONCLUSION: A high TB-HIV co-infection rate was observed in this study. The NTM disease could be misdiagnosed and treated as TB in western Kenya.

ZIEHL-NEELSEN MICROSCOPY IN THE DIAGNOSIS OF TUBERCULOSIS IN SETTINGS OF HIGH HUMAN IMMUNODEFICIENCY VIRUS PREVALENCE.

OBJECTIVE: To determine the accuracy of Ziehl-Neelsen microscopy in the diagnosis of TB in setings of high HIV prevalence. DESIGN: Cross-sectional descriptive study. SETTING: Hospitals serving areas of high human immunodeficiency virus prevalence in western Kenya. The study was conducted between September 2007 and September 2009. RESULTS: In total, 341/872(39.1%) of the TB suspects were positive in ZN, 53.1% (181/341) of them culture positive. Only 3.8% (20/531) of the ZN smear negatives were culture positive. Of the 695 suspects evaluated for both Mycobacterium and HIV infection, 255 (36.7%) were ZN smear positive, 42.7% of them HIV positive. Out of the 440 ZN smear negatives, 37% were HIV positive. Similarly, 168 suspects were culture positive, 46.4% of them HIV positive. The HIV infection did not significantly reduce ZN smear positivity rate (P = 0.42) and culture sensitivity (P = 0.09). The ZN sensitivity and specificity were 88.1% and 79.7%, respectively. The predictive values were 58.0 (PPV), and 95.5% (NPV), respectively. However, the area under the ROC curve was 0.84, with 95% CI between 0.80-0.87 and P < 0.001). The ZN smear microscopy had a lesser ability to distinguish between TB and non-TB cases compared to culture. CONCLUSION: ZN microscopy causes a significant over-diagnosis of TB in settings of high HIV/AIDS prevalence. There is need for further studies on this subject taking into consideration the various confounding factors.

Detection of Mycoplasma genitalium in women with laparoscopically diagnosed acute salpingitis.

OBJECTIVES: Mycoplasma genitalium has been associated with cervicitis, endometritis, and tubal factor infertility. Because the ability of this bacterium to ascend and infect the fallopian tube remains undefined, we performed an investigation to determine the prevalence of M genitalium in fallopian tube, endometrial, and cervical specimens from women laparoscopically diagnosed with acute salpingitis in Nairobi, Kenya. METHODS: Women presenting with pelvic inflammatory disease were laparoscopically diagnosed with salpingitis. Infection with M genitalium in genital specimens was determined by polymerase chain reaction (PCR). RESULTS: Of 123 subjects with acute salpingitis, M genitalium was detected by PCR in the cervix and/or endometrium in nine (7%) participants, and in a single fallopian tube specimen. In addition, those infected with M genitalium were more often HIV infected than women not infected by M genitalium (seven of nine (78%) v 42 of 114 (37%), p<0.03). CONCLUSIONS: M genitalium is able to ascend into the fallopian tube, but its association with tubal pathology requires further investigation.

Non-typhi salmonella in children with severe malaria.

OBJECTIVE: To determine the association between Plasmodium falciparum malaria and non-typhi Salmonella in children. DESIGN: Cross-sectional hospital based study. SETTING: Kilifi District Hospital (KDH) between January 1997 and June 2001. SUBJECTS: Children aged between three months to 123 months (mean age 28.28 months) and who had been admitted to the paediatric or High Dependency Research Ward (HDRW) of the KDH. METHODS: A total of 19, 118 blood cultures routinely obtained for all admissions and 1,820 clinically indicated stools samples were obtained from 9,147 children admitted with malaria. The specimens were cultured and antibiotic sensitivity done using standard laboratory procedures with stringent internal and external quality control in place. RESULTS: The total bacterial pathogens isolated from blood and stool were 1,395/19,118 (7.3%) and 342/1,820 (19%) respectively. Non-typhi salmonella consisted of 260/1,395 (18.6%) of the positive blood cultures and 92/324 (28.4%) of the stool cultures out of which a total of 101 NTS occurred in children with severe malaria. Out of the 9,147 malaria cases admitted, 101/9,147 (1.10%) had concomitant NTS infection. NTS with severe malaria as a proportion of all malaria admissions for the period varied between 0.8% and 1.5%. There was a significant association (p-value=0.032) between clinical outcome of death and female sex of the patient. The NTS isolates which occurred with severe malaria showed various levels of antibiotic resistance. They were resistant to ampicillin (35%), chloramphenicol (18%), gentamicin (22%), cefuroxime (29%), sulphamethoxazole-trimethoprim (39%), ciprofloxacin (3%), cefotaxime (14%), amoxycillin-clavulanic acid (26%) and tobramycin (18.0%). Multidrug resistance (MDR) was seen in 34 (33.6%) of the isolates. CONCLUSIONS: NTS and severe malaria occurring together are a problem in this area and that a large number of the isolates are MDR. An elaborate case-controlled study is required to elucidate the chain of events of both NTS and malaria parasite co-existence.

Chronic diarrhoea among HIV-infected adult patients in Nairobi, Kenya.

OBJECTIVES: Chronic diarrhoea and wasting are well recognized features of AIDS in Africa. However, because of resource constraints few comprehensive aetiological studies have been conducted in sub-Saharan Africa which have included a broad range of microbiological investigations. We undertook a prospective cross-sectional study of adult patients admitted to a government hospital in Nairobi, Kenya, to determine possible bacterial, mycobacterial, parasitic and viral causes of diarrhoea; to consider which may be treatable; and to relate microbiological findings to clinical outcome. METHODS: Stool specimens from 75 consecutive HIV-seropositive patients with chronic diarrhoea admitted to a Nairobi hospital were subjected to microbiological investigation and results were compared with clinical findings and outcome. Stool samples were cultured for bacteria and mycobacteria and underwent light and electron microscopy; lawns of Escherichia coli were probed for pathogenic types and aliquots were tested for the presence of Clostridium difficile cytotoxin. Blood cultures for mycobacteria and other bacterial pathogens were performed as clinically indicated. RESULTS: Thirty-nine (52%) patients yielded putative pathogens, the most common being Cryptosporidium sp. (17%), Salmonella typhimurium (13%), and Mycobacterium tuberculosis (13%). Of 41 patients investigated for pathogenic Escherichia coli, enteroaggregative E. coli and diffusely adherent E. coli were each found in four patients. Thirty-one (41%) patients died. Detection of cryptosporidium cysts was the single most significant predictor of death (X2 = 5.2, P<0.05). Many patients did not improve (21; 28%) or self-discharged whilst still sick (5; 7%) but five (7%) were diagnosed ante mortem with tuberculosis and treated and a further 13 (17%) showed improvement by time of discharge. CONCLUSIONS: HIV-infected patients with chronic diarrhoea in Nairobi have a poor outcome overall, and even with extensive investigation a putative pathogen was identified in only just over half the patients. The most important step is to exclude tuberculosis; and the most useful investigation appears to be Ziehl-Neelsen staining. Other potentially treatable gram-negative bacterial pathogens, S. typhimurium, Shigella sp. and adherent E. coli were, however, common but require culture facilities which are not widely accessible for definitive identification. Further studies focussing on simple ways to identify sub-groups of patients with treatable infections are warranted.

Multidrug-resistant enteroaggregative Escherichia coli associated with persistent diarrhea in Kenyan children.

To study the association of multidrug-resistant enteroaggregative Escherichia coli with persistent diarrhea in Kenyan children, stool specimens were obtained from 862 outpatients under 5 years of age from July 1991 to June 1993. E. coli O44 was identified as the sole bacterial pathogen in four patients experiencing at least 14 days of fever, vomiting, and diarrhea. Disk diffusion testing showed E. coli O44 resistance to tetracycline, ampicillin, erythromycin, trimethoprim-sulphamethoxazole, and amoxicillin/clavulanate and sensitivity to chloramphenicol, nalidixic acid, azithromycin, and cefuroxime. Further studies are needed to clarify the epidemiology, clinical spectrum, and pathogenesis of enteroaggregative E. coli infection.

Effect of piped water supply on human water contact patterns in a Schistosoma haematobium-endemic area in Coast Province, Kenya.

The effect of a piped water supply on human water contact in a Schistosoma haematobium-endemic area in Coast Province, Kenya was studied. After the construction of five community standpipes and one shower unit, there was a 35.1% reduction in the number of people observed using river water, a 44.1% reduction in the frequency of contact with river water, and a 25.4% reduction in the amount of contact. The frequency of river water contact per person also decreased significantly, but the amount of contact per person did not decrease. The total frequency of contact decreased significantly except for washing clothes by the river, washing utensils, and fishing. The frequency per person did not change for most of the activities and significantly increased for washing clothes. The frequency of river water contact in households with high piped water consumption showed a significant decrease compared with those with low piped water consumption. The volume of consumption of piped water was inversely proportional to the distance from the home to the community standpipe. These results indicate that in the study area, the effect of a piped water supply on river water contact behavior was heterologous while the total river water contact decreased significantly, and that the piped water had a beneficial effect on some villagers but very little effect on others.

Epidemiological study on infectious diarrheal diseases in children in a coastal rural area of Kenya.

Diarrheal diseases are major causes of morbidity and mortality among children in developing countries. We have analyzed the causative agents of diarrhea in children under five years of age who resided in rural environments but attended a hospital in Malindi, a coastal town in Kenya. Bacterial diarrhea was found in 239 (27.7%) of 862 patients with diarrhea. Diarrheagenic Escherichia coli, including enteropathogenic, enterotoxigenic, and enterohaemorrhagic strains, was isolated from 119 (13.8%) patients, followed by Salmonella spp. (63 cases, 7.3%) and Shigella spp. (56 cases, 6.5%). Intestinal parasites were found in 109 (12.6%) of the patients. Entamoeba histolytica and Giardia lamblia were found in 67 (7.8%) and 42 (4.9%) of the cases, respectively. Rotavirus was found in 69 (16.1%) of 428 cases, a part of the 862 cases. Significant differences in age distribution were seen in diarrheal cases due to Campylobacter spp., G. lamblia, and rotavirus. No significant seasonal incidence of specific pathogens was found, but the number of diarrheal patients was significantly correlated to rainfall. Drinking water was contaminated with bacteria at concentrations ranging from 10(3) to 10(6) CFU/ml in 98% of the households and by coliform bacteria at concentrations of 10(2) to 10(5) CFU/ml in 72% of the households. These results suggest that the main routes of infection may be contaminated drinking water and fecal-oral transmission of enteric pathogens. Consequently, we propose that the enhancement of hygienic practice through health education is a feasible control measure of diarrhea in the study area.

Outbreak of dysentery Is Kenya due to multi-resistant polyclonal strain of Shigella dysenteriae type 1.

Sixty-eight strains of multi-drug resistant Shigella dysenteriae type 1 were isolated from outbreaks of severe dysentery in three areas of Kenya, namely, Kisumu, Mombassa and Nairobi. The strains were tested for their susceptibility to seven antibiotics. Plasmids were extracted to study their variety and conjugated with Escherichia coli K12 to identify the plasmid coding for the resistance gese. All the strains were resistant to ampicillin, trimethoprim-sulfamethoxazole (S-T), tetracyciine and chloramphenicol. They were sensitive to gentamicin, kanamycin and nalidixic acid. Part of the resistance was found to be plasmid mediated and the sizes of plasmids coding resistance gene wereSMDaand 19MDa. These piasmids coded resistance for ampicillin, trimethoprim-sulfamethoxazole, tetracyciine and chloramphenicol. Verotoxin (VT) production was demonstrated in 80% of the strains by oligonucleotide DNA-DNA gybridization of whole cells with the VT-probe. In view of the extent of drug resistance exhibited by Shigella dysenteriae Type 1 in this study, we recommend the use of nalidixic acid as a first choice of treatment in multiresistant S. dysenteriae Type 1 dysentery outbreaks. Compared to the other two agents that the pathogen was sensitive to, nalidixic acid is relatively cheap with the cost of 7 days treatment for an adult being approximately five US dollars. Resistance to nalidixic acid has to be, however, closely monitored as S. dysenteriae Type 1 has been reported to develop resistance to this drug over time.

Urinary tract infection in patients with short-term indwelling.

Seventy patients (44(62.9%) females) requiring short-term urinary bladder catheterisation at the Kenyatta National Hospital, Nairobi formed the study population. Their mean ages +/- SD was 41+/- 26 years (range 13-100 years). The common indications and objectives for catheterisation included keeping the environment dry (41.1%), relieving urinary retention (27.0%) and urinary incontinence (24.3%). Urinary Tract Infection (UTI) was documented in 48 (68.6%) of the patients. The commonest infection organisms were Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis, the three accounting for 78.6% of the infections. Female gender and increasing age increased the risk of catheter-associated UTI. The risk of having catheter-associated UTI was higher in patients with medical and surgical conditions than in those with obstetric and gynaecology conditions. Patients who were on systemic antibiotics for other conditions acquired UTI less often (27%) than those who were not undergoing antibiotic therapy. The organisms isolated showed marked resistance to commonly available antibiotics. We conclude that UTI, due to resistant organisms, is common in patients undergoing acute urinary bladder catheterisation in our setting and recommend that urinary bladder catheterisation should be avoided whenever possible. In a situation where this is inevitable, closed drainage systems should be used for the shortest duration possible.

Cholera: its story in Africa with special reference to Kenya and other east African countries.

Cholera is an acute often fatal infection whose aetiology, epidemiology, clinical presentation, management, prevention and control are well understood. However, the disease has recently re-emerged as a serious microbial threat due to environmental pressures, increased international travel, population migrations and the emergence of new strains of "old" pathogens. This paper emphasizes, the significance of putting into place quick surveillance methods backed by laboratory services and the importance of creating a rapid response capacity and mechanics to outbreaks.

Bacteriology and sensitivity patterns of pyogenic meningitis at Kenyatta National Hospital, Nairobi, Kenya.

A descriptive cross sectional study on bacteriology and sensitivity patterns of laboratory-proven pyogenic meningitis was carried out over a six month period. A total of 92 patients (52 adults, 40 children) were studied. In 75 (82%) of the cases, the cerebrospinal fluid cultures were bacteriologically positive. Common isolates included Streptococcus pneumoniae (45%), Neisseria meningitidis (14%) and Haemophilus influenzae (12%). Other isolates included Cryptococcus neoformans from four (4.3%) adults who were also HIV-l positive. Sensitivity to antibiotics was determined using the disk diffusion method. There was no resistance to chloramphenicol among the three most common bacterial isolates. However, 7% and 15% of Streptococcus pneumoniae and N. meningitidis isolates, respectively, were resistant to crystalline penicillin. Twenty seven percent of Haemophilus influenzae was resistant to ampicillin. Sensitivity of the three organisms to the third generation cephalosporin (ceftazidime, cefotaxime, ceftriaxone) a second generation cephalosporin (cefuroxime) and augmentin was almost 100%. We recommend that chloramphenicol and crystalline penicillin or ampicillin be initial blind therapy for adults and older children with pyogenic meningitis and ampicillin and chloramphenicol for pre-school children. The above cephalosporins and augmentin are alternative therapy but their use will be limited by cost.

PIP: A total of 92 patients (52 adults and 40 children) admitted to Kenyatta National Hospital in Nairobi, Kenya, with pyogenic meningitis were enrolled in a descriptive cross-sectional analysis of the bacteriology and sensitivity factors associated with this disease. In 75 cases (82%), cerebrospinal fluid cultures were bacteriologically positive. Common isolates included Streptococcus pneumoniae (45%), Neisseria meningitidis (14%), and Haemophilus influenzae (12%). Although all 3 of these isolates were responsive to chloramphenicol, 7% of Streptococcus pneumoniae and 15% of Neisseria menigitidis isolates were resistant to crystalline penicillin and 27% of Haemophilus influenzae isolates were resistant to ampicillin. Sensitivity of these 3 organisms to the third-generation cephalosporins (ceftazidime, cefotaxime, and ceftriaxone), a second-generation cephalosporin (cefuroxime), and augmentin was almost 100%; however, their use is limited by cost. On the basis of these findings, it is recommended that chloramphenicol and crystalline penicillin or ampicillin be initial blind therapy for adults and older children with pyogenic meningitis, while ampicillin and chloramphenicol should be used in preschool children.

Epidemiology of HIV infection among long distance truck drivers in Kenya.

A total number of two hundred eighty three long distance truck drivers and their assistants (loaders) who ferry goods between Kenya and Zaire were included in a cross-sectional study between September 1991 and April 1992. Twenty six percent of the study subjects were seropositive for HIV-1 and none were HIV-2 seropositive. Countries of birth and residence were significantly associated with HIV infection (X2 = 23.6, P = 0.0006). Significant associations were also found between HIV seropositivity and level of education from secondary school and above (OR = 3.4, 95% C.I. = 1.01-11.55); being circumcised was more protective, (OR = 0.38; 95% C.I. = 0.19-0.76), history of many years of driving (X2 = 9.3, p = 0.0254) and income (OR = 11.13, 95% C.I. = 1.35-91.95). When a stepwise multiple logistic regression model was fitted to all the variables observed to be significant in the univariate analysis, the following risk factors attained statistical significance: lack of circumcision (OR = 3.75); income greater than Ksh. 2000 (OR = 7.24); being employed in long distance driving more than 11 years (OR = 3.98); and secondary school education and above (OR = 4.06, 95% C.I. = 1.18-13.98). Reference for all the above Odds Ratios was 1.

PIP: A total number of 283 long distance truck drivers and their assistants (loaders) who ferry goods between Kenya and Zaire were included in a cross-sectional study between September 1991 and April 1992. 26% of the study subjects were seropositive for HIV-1 and none were HIV-2 seropositive. Countries of birth and residence were significantly associated with HIV infection (chi square = 23.6, p = 0.0006). Significant associations were also found between HIV seropositivity and level of secondary school education and above (OR = 3.4, 95% CI = 1.01-11.55); being circumcised, which was more protective (OR = 0.38, 95% CI = 0.19-0.76); a history of many years of driving (chi square = 9.3, p = 0.0254); and income (OR = 11.13, 95% CI = 1.35-91.95). When a stepwise multiple logistic regression model was fitted to all the variables observed to be significant in the univariate analysis, the following risk factors attained statistical significance: lack of circumcision (OR = 3.75); income greater than Ksh. 2000 (OR = 7.24); being employed in long distance driving more than 11 years (OR = 3.98); and secondary school education and above (OR = 4.06, 95% CI = 1.18-13.98). Reference for all the above odds ratios was 1.

Infection and morbidity in patients with tuberculosis in Nairobi, Kenya.

OBJECTIVE: To examine the role of acute infection as a cause of morbidity in patients with tuberculosis. DESIGN: Cross-sectional documentation of predefined acute morbid events. SETTING: Infectious Diseases Hospital, Nairobi, Kenya. PATIENTS: Adults (> or = 15 years), inpatients and outpatients with a diagnosis of tuberculosis presenting with one or more of a series of clinical features. A new event was defined as one occurring at least 1 week after the initial event. INTERVENTIONS: Patients' treatment was modified depending on the results of laboratory investigations. MAIN OUTCOME MEASURES: There were 642 events from 398 patients, 235 HIV-positive patients had 438 events and 163 HIV-negative patients had 204 events (P < 0.0001). Forty-two out of the 235 (18%) HIV-positive patients were bacteraemic compared with nine out of the 163 (6%) HIV-negative patients (P = 0.0003). The most common isolates from blood were Salmonella typhimurium and Streptococcus pneumoniae. RESULTS: Faecal specimens were obtained more commonly from HIV-positive patients (P < 0.001), and often contained bacterial pathogens. CONCLUSIONS: Many of the causes of morbidity in patients with tuberculosis and HIV are not due to tuberculosis or antituberculous therapy, and will not be identified without microbiological investigation.

PIP: Tuberculosis (TB) is a common complication of HIV in Africa. A 1988-89 study further confirmed that considerable morbidity and mortality from acute bacterial infection occurred in HIV patients. It has also been found that anti-TB therapy seems to be as effective in HIV-positive as in HIV-negative TB patients. This paper reports on the level and nature of infectious morbidity suffered by HIV-positive patients receiving treatment for TB. The assessment is based upon a sample of inpatients and outpatients at the Infectious Diseases Hospital in Nairobi. Patients were aged 15 years and older, with a TB diagnosis presenting with 1 or more of a series of clinical features. 642 morbid events were seen in 398 patients: 235 HIV-positive patients had 438 event and 163 HIV-negative patients had 204 events. 18% of the HIV-positive patients versus 6% of the HIV-negative patients were bacteremic. Salmonella typhimurium and Streptococcus pneumoniae were most commonly isolated from sera, while fecal specimens were obtained more commonly from HIV-positive patients and often contained bacterial pathogens. The authors conclude that many causes of morbidity in patients with TB and HIV are not due to TB or anti-TB therapy and will not be identified without microbiological investigation. These results suggest that even with effective anti-TB chemotherapy HIV-positive patients will remain or become unwell.

Anti-tuberculous initial drug resistance of Mycobacterium tuberculosis in Kenya: a ten-year review.

Our experience at the Respiratory Diseases Research Unit (RDRU), over the last 10 years (1981-1990) on the initial drug resistance pattern, focusing on three drugs viz: isoniazid (H), streptomycin (S) and rifampicin (R) is presented. Records on all isolates of M. tuberculosis from one specimen of every newly diagnosed patient recruited countrywide between 1981-1990 were reviewed. We analyzed records of 6,514 isolates and found that total resistance to the three drugs had increased from 8.9% to 14.4%. Resistance to H alone increased from 6.8% to 10.2% while that of S alone from 0.8% to 1.8%. Resistance to R was between 0.1% and 0.3%. Generally, the increase in the resistance trend to both H and S was statistically significant (p = < 0.05 and 0.03, respectively). Although in our analysis we did not address the possible impact of HIV infection, we hope that these findings form a basis for evaluation of this and other possible factors on the emergence of anti-TB drug resistance in future studies.

PIP: A retrospective review of medical records of 6514 Mycobacterium tuberculosis isolates of newly diagnosed patients at the Respiratory Diseases Research Unit of the Kenya Medical Research Institute between 1981 and 1990 aimed to determine the initial drug-resistance pattern for isoniazid, streptomycin, and rifampicin. Overall resistance increased from 8.9 to 14.4% (p 0.001). The increase in the resistance trend to isoniazid and to streptomycin were statistically significant (6.8-10.2; p 0.05 and 0.8-1.8; p = 0.03, respectively) as well as the trend among isolates resistant to both isoniazid and streptomycin (1.2.4; p = 0.03). The trend was more pronounced during 1987-1990 than during 1981-1986. There was no trend in the resistance to rifampicin alone (0.1-0.3%). Just 4 isolates were resistant to both isoniazid and rifampicin. Only 1 was resistant to both streptomycin and rifampicin. None were resistant to all 3 antibiotics. These first-line drugs are used widely in Kenya. These rates of initial resistance to the drugs are lower than those in other developing countries. The lower resistance rate is unlikely to continue, however, due to higher prevalence of HIV infection and the associated increase in tuberculosis incidence. These findings provide researchers a baseline with which to study M. tuberculosis drug resistance and other risk factors as drug resistance increases in Kenya.