The microbiological diagnosis of tuberculosis in a resource - limited setting: is acid-fast bacilli microscopy alone sufficient?

The objective of this study is to audit the processes for the microbiological diagnosis of tuberculosis (TB) in our resource-limited setting. A total of 694 specimens were received from 333 patients. 129 (38.7%) of these patients were positive for TB. 78 (60.5%) were positive on AFB microscopy alone, 13 (10.0%) on culture alone and 38 (29.5%) on both culture and AFB microscopy. Fifty-one (51) cases were positive on culture, 38 of these (74.5%) had growth on Lowensen-Jensen culture medium alone, 11 (19.6%) on Pyruvic Acid Enhanced Medium (PAEM) and 3 (5.9%) on both culture media. AFB microscopy showed a diagnostic specificity of 71.6% and a sensitivity of 74.5%. M. Bovis appears to be prevalent and we suggest the need for speciation. If AFB microscopy is to be routinely used alone, without confirmation by culture, then the overriding need is for quality to be fully assured in its use.Keywords: Mycobacteria, tuberculosis, accuracy, AFB microscopy, cultur

Epidemiology of Smear ‐ Negative Tuberculosis in Ibadan, Nigeria

Inadequate case detection has been identified as one of the reasons for high burden of tuberculosis (TB) in the world especially in poor resourced countries of Africa and Asia. This retrospective laboratory study involving the review of specimens processed at the TB laboratory of the Department of Medical Microbiology and Parasitology, University College Hospital, Ibadan, Nigeria was carried out over a period of five years (January 2006‐December 2010) to access the epidemiology of smear‐ negative TB. Of the 3468 specimens processed, 2,175 (62.7%) were from males while a lower percentage (37.3%)1293 were from females, giving a M:F = 1:0.37. Over half of the specimens, 2,046 (59.0%) were from patients aged 21 to 60 years, 392 (11.3%) from 11 to 20 years, 825 (23.8%) from 60 years and above while 205 (5.9%) were from age 1‐10 years. Most of the 2,663 (76.8%) specimens processed were sputum while 201 (5.8%) were gastric washings. Three hundred and nine (8.9%) were smear positive while 392 (11.3%) out of the 3468 specimens processed were culture positive. However, 83 (2.6%) of the 3159 smearnegative specimens were culture positive (false negative) while 66 (21.4%) of the 309 smear‐ positive specimens were negative for culture (false positive). The majority, 3010 (86.8%) were smear and culture negative while 309 (8.9%) were positive for both tests. Of the 83 false negative specimens, 51 were sputum samples representing (61.4%), 19 (22.9%) were gastric washings while 13 (15.7%) were from extra‐pulmonary sites (CSF, aspirates, ascitic fluids, etc). The findings of 2.6% smear‐negative but culture positive (false negative) specimens in this study reveals that culture of specimens in addition to smear microscopy from suspected cases is necessary as a diagnostic /confirmatory tool for tuberculosis.Keywords: Epidemiology, Smear negative, TB, Ibadan, Nigeri

EPIDEMIOLOGY OF SMEAR - NEGATIVE TUBERCULOSIS IN IBADAN, NIGERIA

Inadequate case detection has been identified as one of the reasons for high burden of tuberculosis (TB) in the world especially in poor resourced countries of Africa and Asia. This retrospective laboratory study involving the review of specimens processed at the TB laboratory of the Department of Medical Microbiology and Parasitology, University College Hospital, Ibadan, Nigeria was carried out over a period of five years (January 2006-December 2010) to access the epidemiology of smear- negative TB. Of the 3468 specimens processed, 2,175 (62.7%) were from males while a lower percentage (37.3%)1293 were from females, giving a M:F = 1:0.37. Over half of the specimens, 2,046 (59.0%) were from patients aged 21 to 60 years, 392 (11.3%) from 11 to 20 years, 825 (23.8%) from 60 years and above while 205 (5.9%) were from age 1-10 years. Most of the 2,663 (76.8%) specimens processed were sputum while 201 (5.8%) were gastric washings. Three hundred and nine (8.9%) were smear positive while 392 (11.3%) out of the 3468 specimens processed were culture positive. However, 83 (2.6%) of the 3159 smear-negative specimens were culture positive (false negative) while 66 (21.4%) of the 309 smear- positive specimens were negative for culture (false positive). The majority, 3010 (86.8%) were smear and culture negative while 309 (8.9%) were positive for both tests. Of the 83 false negative specimens, 51 were sputum samples representing (61.4%), 19 (22.9%) were gastric washings while 13 (15.7%) were from extra-pulmonary sites (CSF, aspirates, ascitic fluids, etc). The findings of 2.6% smear-negative but culture positive (false negative) specimens in this study reveals that culture of specimens in addition to smear microscopy from suspected cases is necessary as a diagnostic /confirmatory tool for tuberculosis

Evaluation of the comparative efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and artesunate-amodiaquine-chlorpheniramine (Artemoclo™) for the treatment of acute uncomplicated malaria in Nigerian children.

OBJECTIVE: To evaluate the comparative efficacy and safety of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) and artesunate-amodiaquine-chlorpheniramine (AQC) for the treatment of acute uncomplicated malaria among Southwest Nigerian children. SUBJECTS AND METHODS: One hundred and sixty children aged 6 months to 14 years with acute uncomplicated malaria were randomized to AL (n = 53), ASAQ (n = 53), or AQC (n = 54). Enrollees were seen daily on days 0-3 and then on days 7, 14, 21, 28 and 42 for clinical and parasitological evaluations. Paired samples of genomic DNA at enrolment and at the time of recurrent parasitaemia were genotyped using nested PCR to distinguish between reinfection and recrudescence. Detailed haematological and biochemical evaluations were carried out in a subset of enrollees on days 0, 7 and 28 as part of a safety evaluation. RESULTS: Of the 160 children, 144 (90%) completed the study. The mean fever clearance times and parasite clearance times for AL, ASAQ and AQC were comparable (p = 0.94 and p = 0.122, respectively). On day 14, the adequate clinical and parasitological response (ACPR) for AL and AQC was 100% and for ASAQ it was 90% (p = 0.39). The PCR-uncorrected results on days 28 and 42 and the ACPR-corrected results on day 42 were similar for all drugs (p = 0.62 and p = 0.56, respectively). AQC resulted in the best parasite clearance and haematological recovery on day 2 (p = 0.022 and p = 0.018, respectively). Biochemical parameters were not adversely affected by the three artemisinin-based combination therapies (ACTs) and these were well tolerated. CONCLUSION: The three ACTs were efficacious and safe, but AQC resulted in a better haematological recovery on day 2 and higher cure rates throughout the study period

Contributions of malaria, helminths, HIV and iron deficiency to anaemia in pregnant women attending ante-natal clinic in SouthWest Nigeria

Background: Iron deficiency is a dominant source of anaemia in many settings. To evaluate the key cause of anaemia in the study area, the prevalence of anaemia due to major public health diseases was compared with anaemia due to iron deficiency. Methods: Pregnant women were recruited from ante-natal (n=490) and HIV clinics (n=217) with their personal data documented using a questionnaire. Microscopy of Giemsa-stained thick smears was used for detection of malaria parasites while helminths in stools were detected using direct smear method. Haematocrit values were determined by capillary method. Serum ferritin levels were determined using enzyme-linked immunosorbent assay. Data was analysed using SPSS version 22.0. Results: The mean age of the recruited women was 28.6\ub15.4 years old. There were 68.1% cases of anaemia of which 35.5% was due to infections only predominantly HIV and malaria, 14.9% from unknown sources while anaemia due to iron deficiency only was 7.1%. Conclusion: It can safely be inferred that malaria and HIV predispose to anaemia than iron deficiency in the study area. Although pregnant women are dewormed and given IPTp for helminths and malaria treatment respectively, there should be complementary routine malaria screening at ANC visits for those with HCT values <33% and those infected with HIV

Molecular epidemiology of pneumococci obtained from Gambian children aged 2–29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine

BACKGROUND: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children METHODS: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. RESULTS: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618. CONCLUSION: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia

Baseline study for improving diagnostic stewardship at secondary health care facilities in Nigeria

Background: Blood culture diagnostics are critical tools for sepsis management and antimicrobial resistance (AMR) surveillance. A baseline study was conducted to assess reported sepsis case finding, blood culture diagnostics, antimicrobial susceptibility testing (AST) and antimicrobial use at secondary health care facilities to inform the development of diagnostic stewardship improvement strategies in Nigeria. Methods: A cross-sectional online survey was conducted among 25 public secondary health care facilities in Abuja, Federal Capital Territory (FCT) and Lagos State in Nigeria to evaluate the capacity for pathogen identification and AST. Data were then prospectively extracted on all patients with reported suspected sepsis from electronic medical records from selected departments at two facilities in the Federal Capital Territory from October 2020 to May 2021 to further assess practices concerning sepsis case-finding, clinical examination findings, samples requested, and laboratory test results. Data were descriptively analysed, and a multivariate logistic regression analysis was conducted to determine factors associated with blood culture requests. Results: In the online survey, 32% (8/25) of facilities reported performing blood cultures. Only one had access to a clinical microbiologist, and 28% (7/25) and 4% (1/25) used standard bacterial organisms for quality control of media and quality control strains for AST, respectively. At the two facilities where data abstraction was performed, the incidence of suspected sepsis cases reported was 7.1% (2924/41066). A majority of these patients came from the paediatrics department and were outpatients, and the median age was two years. Most did not have vital signs and major foci of infection documented. Blood cultures were only requested for 2.7% (80/2924) of patients, of which twelve were positive for bacteria, mainly Staphylococcus aureus. No clinical breakpoints were used for AST. Inpatients (adjusted odds ratio [aOR]: 7.5, 95% CI: 4.6–12.3) and patients from the urban health care facility (aOR:16.9, 95% CI: 8.1–41.4) were significantly more likely to have a blood culture requested. Conclusion: Low blood culture utilisation remains a key challenge in Nigeria. This has implications for patient care, AMR surveillance and antibiotic use. Diagnostic stewardship strategies should focus on improving access to clinical microbiology expertise, practical guidance on sepsis case finding and improving blood culture utilisation and diagnostics.Peer Reviewe

Consequences of restricting antimalarial drugs to rapid diagnostic test-positive febrile children in south-west Nigeria.

OBJECTIVES: To investigate the consequence of restricting antimalarial treatment to febrile children that test positive to a malaria rapid diagnostic test (MRDT) only in an area of intense malaria transmission. METHODS: Febrile children aged 3-59 months were screened with an MRDT at health facilities in south-west Nigeria. MRDT-positive children received artesunate-amodiaquine (ASAQ), while MRDT-negative children were treated based on the clinical diagnosis of non-malaria febrile illness. The primary endpoint was the risk of developing microscopy-positive malaria within 28 days post-treatment. RESULTS: 309 (60.5%) of 511 children were MRDT-positive while 202 (39.5%) were MRDT-negative at enrolment. 18.5% (50/275) of MRDT-positive children and 7.6% (14/184) of MRDT-negative children developed microscopy-positive malaria by day 28 post-treatment (ρ = 0.001). The risk of developing clinical malaria by day 28 post-treatment was higher among the MRDT-positive group than the MRDT-negative group (adjusted OR 2.74; 95% CI, 1.4, 5.4). A higher proportion of children who were MRDT-positive at enrolment were anaemic on day 28 compared with the MRDT-negative group (12.6% vs. 3.1%; ρ = 0.001). Children in the MRDT-negative group made more unscheduled visits because of febrile illness than those in MRDT-positive group (23.2% vs. 12.0%; ρ = 0.001). CONCLUSION: Restricting ACT treatment to MRDT-positive febrile children only did not result in significant adverse outcomes. However, the risk of re-infection within 28 days was significantly higher among MRDT-positive children despite ASAQ treatment. A longer-acting ACT may be needed as the first-line drug of choice for treating uncomplicated malaria in high-transmission settings to prevent frequent re-infections

Evaluation of the efficacy and safety of artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in Nigerian infants and children

<p>Abstract</p> <p>Background</p> <p>The six-dose regimen of artemether-lumefantrine (AL) is now considered the gold standard for the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria. There are few reports evaluating co-artemether in very young Nigerian infants and children. Results of the evaluation of the six-dose regimen in very young infants and children in Nigeria are presented in this report.</p> <p>Methods</p> <p>As part of a larger African study, this open label, non-comparative trial, assessed the efficacy and safety of six-dose regimen of AL tablets in 103 Nigerian infants and children weighing between five and 25 kg suffering from acute uncomplicated malaria. Treatment was administered under supervision over three days with children as in-patients. 12-lead ECG tracings were taken pre-treatment and at day 3.</p> <p>Results</p> <p>Ninety-three infants and children completed the study as stipulated by the protocol. Mean fever and parasite clearance times for the intent to treat population (ITT) were 24.9 h ± (1.28) and 26 h ± (4.14) and the corresponding figures for the per-protocol population (PP) were 19.24 h ± 13.9 and 25.62 h ± 11.25 respectively. Day 14 cure rates for the ITT and PP were 95.1% and 100% respectively while day 28 cure rates were 91.3% and 95.7% respectively. The overall PCR corrected day 28 cure rate was 95.1% for the ITT. The six-dose regimen of AL was well tolerated with no drug-related serious adverse events. Although six patients recorded a QTc prolongation of > 60 ms on D3 over D0 recording, no patient recorded a QTc interval > 500 ms.</p> <p>Conclusion</p> <p>The six-dose regimen of AL tablets is safe and effective for the treatment of acute uncomplicated malaria in Nigerian infants and children weighing between five and 25 kg.</p> <p>Trial registration</p> <p>NCT00709969</p